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TerminatedNCT03173950Updated Oct 27, 2026Results posted

Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers

A Phase 2 interventional study of Nivolumab and EKG in Medulloblastoma, Ependymoma and Pineal Region Tumors, sponsored by National Cancer Institute (NCI). Terminated at 3 sites in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-10-27.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Why this study was terminated
Support was withdrawn from study resulting in early termination of study. Investigator had to close study due to no drug supply.
Updated Oct 27, 2026Study documents postedPosted results revisedGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
136
Allocation
Not applicable
Ages
18 Years to 99 Years
Sex
All
01

Study summary

Background:

More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. This study will test whether the immunotherapy drug nivolumab is an effective treatment for people with rare CNS tumors.

Objectives:

To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread.

Eligibility:

Adults whose rare CNS tumor has returned.

Design:

Individuals will be screened:

  • Heart and blood tests
  • Physical and neurological exam
  • Hepatitis tests
  • Pregnancy test
  • Magnetic resonance imaging (MRI). They will lay in a machine that takes pictures.
  • Tumor tissue sample. This can be from a previous procedure.

At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life.

Individuals will get nivolumab in a vein every 2 weeks for up to 64 weeks.

Individuals will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life.

Genetic tests will be done on individuals' tumor tissue. Individuals will be contacted if any clinically important results are found.

After treatment ends, individuals will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....

Read the detailed description

Background:

  • There are more than 130 identified primary tumors of the central nervous system (CNS). Most have an annual incidence of less than 1000 in the United States.
  • Given the rarity of each of the tumors listed above, there is a paucity of proven therapies. Most of these neoplasms are treated with maximum surgical resection followed by treatment with external beam radiotherapy. With few exceptions (medulloblastoma, adult ependymoma), there are no effective systemic regimens and even in chemotherapy sensitive disease, most patients with recurrence eventually have no remaining salvage treatments available.
  • In the setting of this unmet need, we propose to create a basket protocol that will evaluate the efficacy of the programmed cell death protein 1 (PD-1) inhibitor, nivolumab, in patients with refractory rare central nervous system neoplasms.
  • This study seeks to establish effective therapies at recurrence in patients with rare CNS tumors. We hypothesize that this therapy will improve progression free survival and/or objective responses.
  • It will be important to determine whether any determined survival benefit is associated with improvements in symptoms or does a worsening of symptoms offset the increase in survival. Precedence exists for measuring non-therapeutic endpoints in oncology research, and specifically in studies evaluating therapeutic benefit in patients with CNS tumors. There have been efforts in neuro-oncology to evaluate secondary endpoints using validated instruments as an additional indicator of benefit. The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Spine Tumor Module (MDASI-SP) allow for the self-reporting of symptom severity and interference with daily activities for patients with either brain or spinal cord tumors. The availability of validated instruments provides an opportunity to prospectively assess the impact of treatment, both positive and negative on patients.

Objective:

Determine the efficacy of nivolumab in a variety of recurrent, refractory primary central nervous system tumors as measured by disease control rate (confirmed complete response (CR)/partial response (PR) or durable stable disease (SD) for at least 6 months).

Eligibility:

  • Documented recurrent or progressive disease that corresponds to one of the tumors eligible for testing.
  • Age >= 18 years of age.
  • Karnofsky Performance >= 70%.
  • Tumor tissue available for central review to confirm morphologic diagnosis
  • Tumor tissue or slides must be available for central molecular and immune profiling.

Design:

  • This is an open label phase II clinical trial. Patients will be treated with the immune checkpoint inhibitor, nivolumab, at a standard dose of 240 mg intravenously every 2 weeks (+/- 3 days) for cycles 1 through 2, then doses of 480 mg every 4 weeks (+/- 3 days) for a total of 14 additional doses (cycles). A maximum of 18 treatments will be given (64 weeks).
  • A cycle will be defined as 4 weeks and patients will undergo efficacy assessments using MR imaging (and/or other imaging tests if applicable) every 2 cycles. Toxicity assessments will occur before the initiation of each cycle and patient outcomes measures (PROs) will be completed at the time of each imaging study (every 2 cycles) but prior to the patient being informed of the imaging results.
  • After completion of the planned treatment course or if treatment was stopped because of toxicity, patients will undergo imaging evaluations and PRO measurements every 8 weeks (or 2 months) for one year, then every 3 months for the next year, then every 4

months for the next year and then every 6 months while the patient remains on the protocol. Patients off treatment because of disease progression will not undergo future imaging or PRO assessments on this protocol.

  • Bayesian Optimal Phase 2 design (BOP2), will be used to conduct this phase II trial in patients with a variety of recurrent, refractory primary central nervous system tumors.
  • The study will be comprised of 2 disease cohorts: heavily pretreated (defined as having received 3 or more prior therapies) and non-heavily pretreated (defined as having received up to 2 prior therapies). Each cohort will be evaluated independently for efficacy.
02

Conditions studied

  • Medulloblastoma
  • Ependymoma
  • Pineal Region Tumors
  • Choroid Plexus Tumors
  • Atypical/Malignant Meningioma

Keywords

  • Immunotherapy
  • Anti-PD-1 Antibody
  • Brain Tumors
  • MDASI-BT
  • Spinal Cord Tumors
03

In context

Medulloblastoma

317 studies on the registry are indexed under Medulloblastoma; 51 are open to participants now.

This study's enrollment of 136 is above the median of 31 across 255 interventional studies indexed under Medulloblastoma.

Browse Medulloblastoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Histopathologically proven diagnosis of Ependymoma, Medulloblastoma, Parenchymal Pineal Region Tumors (Pineoblastoma, Pineocytoma, Pineal Tumor of Intermediate Differentiation, Papillary Tumor of the Pineal Region), Choroid Plexus Tumors (Carcinoma, Papilloma, Atypical Papilloma), Histone Mutated Gliomas, Gliomatosis Cerebri, Atypical Teratoid/Rhabdoid Tumor (ATRT), Malignant/Atypical Meningioma*, Gliosarcoma or Primary CNS Sarcoma, Pleomorphic Xanthoastrocytoma (PXA) and Anaplastic Pleomorphic Xanthoastrocytoma (APXA), and tumors formerly known as Primitive Neuro-Ectodermal Tumors (Embryonal Tumor with Multilayered Rosettes, Medulloepithelioma, Central Nervous System (CNS) Neuroblastoma, CNS Ganglioneuroblastoma, CNS Embryonal Tumor NOS; and tumor entities emerging from methylation profiling of CNS-PNETs: CNS neuroblastoma with Forkhead box protein R2 (FOXR2) activation, CNS Ewing sarcoma family tumor with CIC alteration, CNS high-grade neuroepithelial tumor with meningioma 1 (MN1) alterations, and CNS high-grade neuroepithelial tumor with BCOR alteration) prior to registration.

    *Individuals with extra from meningioma will be eligible even if pathology review fails to demonstrate high grade features on available tumor samples.

  • The tumor tissue (e.g., block or 20 unstained slides) must be available to be sent for immunophenotyping by National Cancer Institute (NCI) Laboratory of Pathology.
  • Individuals must have progressive tumor growth after having received established standard of care and/or other experimental treatments for their newly diagnosed or recurrent disease. Individuals will be enrolled into 2 different cohorts (cohort 1 or heavily pretreated; cohort 2 or not heavily pretreated).
  • Age >= 18
  • performance status >= 70 within 14 days prior to Step 2 registration; Individuals with severe paraparesis/paraplegia who need minimal assistance for selfcare due to their motor deficit but are otherwise functionally independent will be considered eligible.

  • Adequate hematologic function based on complete blood count (CBC)/differential within 14 days prior to Step 2 registration defined as follows:

    • >= 1,500 cells/mm\^3;
    • count >= 100,000 cells/mm\^3
    • > 9.0 g/dl (may be transfused to achieve this level)

  • Adequate renal function within 14 days prior to Step 2 registration defined as follows:

    • Blood urea nitrogen (BUN) \<= 30 mg/dl and
    • Serum creatinine \<= 1.7 mg/dl

Note: If the serum creatinine is greater than 1.7 mg/dl, a 24-hour urine will be obtained and if the result of this study is within normal limits*, the patient would be eligible to enroll onto study. (*Normal Creatinine Clearance Range: Male: 90 - 130 ml/min; Female: 80 - 125 ml/min)

  • Adequate hepatic function within 14 days prior to Step 2 registration defined as follows:

    • Total (except patients with Gilbert's Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) \<= 2.0 mg/dl and
    • (ALT) and aspartate aminotransferase (AST) \<= 2.5x
  • No active or chronic hepatitis infection. virus (HCV) antibody (for Hepatitis C) and Surface antigen and Hepatitis B core antibody must be negative. This has been routinely incorporated into immunotherapy trials with because of concerns that the risk of treatment-induced hepatic injury is increased in the setting of active viral hepatitis.
  • The individual must not be on a dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent.
  • The individual must provide study-specific prior to study entry. No Durable Power of Attorney or Next of Kin can provide initial consent.
  • The effects of nivolumab on the developing human fetus are unknown. For this reason, women of (WOCBP) must use appropriate method(s) of . WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of drug.

NOTE: Based on the evidence cited in Nivolumab IB ver. 20, given that nivolumab is not a genotoxic agent, and that relevant systemic concentrations sufficient to produce a risk of fetal toxicity are not expected in individuals of childbearing potential (IOCBP) partners from exposure to an individual's seminal fluid, men that can father children will not be required to use contraceptive measures and/or a latex or other synthetic condom during sexual activity with an WOCBP partner.

Exclusion criteria

EXCLUSION CRITERIA:

  • Individuals who are receiving any other agents.
  • Prior use of an immunotherapy such as (but not limited to) a vaccine therapy, dendritic cell vaccine, other , or intracavitary or convectional enhanced delivery of chemotherapy.
  • Prior or concurrent unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.

  • Severe, active co-morbidity defined as follows:

    • Unstable angina within the last 6 months prior to Step 2 registration.
    • Transmural myocardial infarction within the last 6 months prior to Step 2 registration.
    • Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an (EKG) performed within 14 days prior to Step 2 registration.
    • grade II or greater congestive heart failure requiring hospitalization within 12 months prior to Step 2 registration.
    • History of stroke, cerebral vascular accident (CVA) or within 6 months prior to Step 2 registration, with the exception of pericavitary ischemia due to tumor resection.
    • Serious and inadequately controlled cardiac arrhythmia.
    • Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or peripheral vascular disease.
    • Evidence of bleeding diathesis or coagulopathy.
    • Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, major surgical procedure, open , or significant traumatic injury within 28 days prior to Step 2 registration, with the exception of the craniotomy for tumor resection.
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
    • exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
    • Known acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that (HIV) testing is not required for entry into this protocol. The need to exclude participants with acquired immunodeficiency syndrome (AIDS) is based on the lack of information regarding the safety of nivolumab in patients with active HIV infection.
    • Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for immunologic toxicity.
  • Individuals with active disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic , should be excluded. These include but are not limited to individuals with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or chronic inflammatory demyelinating polyneuropathyI (CIDP), myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and individuals with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.

Of note, individuals with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Participants with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible. However, individuals with vitiligo, diabetes mellitus, and Hashimoto thyroiditis on appropriate replacement therapy may be enrolled.

  • Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
  • Allergies and Adverse Drug Reaction: History of allergy to study drug components.
  • Pregnancy or lactating women due to possible adverse effects on the developing fetus or infant due to study drug. Women of must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) within 24 hours prior to Step 2 registration.
  • History of severe reaction to any monoclonal antibody.
  • Individuals unable to have magnetic resonance imaging (MRIs).
Terms in these criteria, in plain language(27)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

COPD

Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
136 participants (actual)

Study arms

  • Experimental
    Arm 1/Experimental Therapy - Nivolumab

    Individuals will receive nivolumab at standard dose of 240 mg intravenous (IV) every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses.

    Drug: Nivolumab · Diagnostic Test: EKG · Diagnostic Test: MRI Brain and/or spine · Diagnostic Test: Body CT Scan · Other: MDASI-BT · Other: MDASI-SP

Interventions

  • DrugNivolumab

    Individuals will receive nivolumab at standard dose of 240 mg intravenous (IV) every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses.

    Also known as: Opdivo

  • Diagnostic testEKG

    Screening/baseline.

    Also known as: Electrocardiogram

  • Diagnostic testMRI Brain and/or spine

    Screening/baseline.

    Also known as: Magnetic resonance imaging brain and/or spine

  • Diagnostic testBody CT Scan

    Screening/baseline.

    Also known as: Body computed tomography

  • OtherMDASI-BT

    Screening/baseline. During active treatment and post therapy follow up.

    Also known as: M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT)

  • OtherMDASI-SP

    Screening/baseline. During active treatment and post therapy follow up.

    Also known as: M.D. Anderson Symptom Inventory Spine Tumor (MDASI-SP)

06

What researchers measure

Primary outcomes

  1. Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation

    Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (\>25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by

    Time frame: From cycle one Day 1 of the treatment through the end of treatment, up to 64 weeks

  2. Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With a 95% Confidence Interval

    Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (i.e., \>25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by

    Time frame: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks

  3. Progression Free Survival (PFS)

    PFS is defined as the date of on-study to the date of disease progression or death, estimated with the Kaplan-Meier method and reported with a 95% confidence interval. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is \>25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids.

    Time frame: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks

  4. Progression Free Survival at 6 Months With 95% Confidence Interval

    PFS-6 is the rate of durable Stable Disease lasting at least 6 months defined from the day of study entry until imaging is confirmed to show disease progression reported with a 95% confidence interval based on the Brookmeyer-Crowley method. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is \>25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids.

    Time frame: 6 months after the initiation of treatment, up to 24 weeks

Secondary outcomes

  1. Overall Survival (OS)

    OS is defined as the date of on-study to the date of death from any cause or last follow up, estimated with the Kaplan-Meier method and reported with a 95% confidence interval based on the Brookmeyer-Crowley method.

    Time frame: Time from the study entry and after initiation of nivolumab to participants death, up to 5 years

  2. Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With a 95% Confidence Interval, at Each Time Point

    Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference.

    Time frame: Baseline (Up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)

  3. Mean Symptom Burden Severity & Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) & MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With Standard Deviation(SD) at Each Time Point

    Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference.

    Time frame: Baseline (up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, or 12 (one cycle = 4 weeks)

  4. Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With 95% Confidence Interval

    Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Higher scores indicate. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Response status was determined by whether disease progression occurred prior to or at cycle 6 or not. Participants who had disease progression prior to or at cycle 6 were non-responders and participants who did not have disease progression by cycle 6 were responders. Relevant MDASI-BT \& MDASI-SP data are those that correspond to the cycle where response status was determined. It is a unique cycle for each participant.

    Time frame: Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.

  5. Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With Standard Deviation

    Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Higher scores indicate. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Response status was determined by whether disease progression occurred prior to or at cycle 6 or not. Participants who had disease progression prior to or at cycle 6 were non-responders and participants who did not have disease progression by cycle 6 were responders. Relevant MDASI-BT \& MDASI-SP data are those that correspond to the cycle where response status was determined. It is a unique cycle for each participant.

    Time frame: Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.

  6. Mean Change Scores in Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Between Baseline and Even-numbered Cycle

    Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Mean change score is even-numbered cycle minus baseline. Hence, negative change scores indicate improvement.

    Time frame: Between Baseline (up to 14 days prior to treatment) and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)

  7. Number of Grades 1, 2, 3, 4, and/or 5 Treatment Related Serious and/or Non-serious Adverse Events and Type

    Here is the number of Grade 1, 2, 3, 4, and/or 5 serious and/or non-serious adverse events and type assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

    Time frame: Adverse Events were monitored/assessed from the first study intervention, Study Day 1 through 100 days after the study agent was last administered, up to 5 years

Other outcomes

  1. Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

    Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Time frame: Adverse Events were monitored/assessed from the first study intervention, Study Day 1 through 100 days after the study agent was last administered, up to 5 years

07

Results

Posted Aug 18, 2026
Limitations and caveats
11 participating sites started/3completed:National Institutes of Health Clinical Center, Northwestern University, University of Texas MDAnderson Cancer Center. Sites contributed to data/closed early to enrollment due to poor accrual:University of Pittsburgh Medical Center, University of California San Diego, University of California Irvine, Orlando Health, Washington University in St. Louis, NorthShore University HealthSystem, The Ohio States University, and Medical University of South Carolina.

Participant flow

Participant flow — Overall Study
MilestoneCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Started763030
Lost to further follow-up230
Refused further follow-up120
Completed treatment phase but refused the protocol specified follow-up100
Death during follow-up period3990
Completed42140
Not completed341630
Withdrew: Ineligible0019
Withdrew: Pursuing other treatment001
Withdrew: Participant declined to participate (before treatment started).019
Withdrew: Refused further treatment110
Withdrew: Physician decision1270
Withdrew: National cancer institute and principal investigator discretion010
Withdrew: Study closure/termination1550
Withdrew: Death on study310
Withdrew: Withdrew informed consent form and decided not to participate001
Withdrew: Did not complete a minimum of one cycle of treatment300

Outcome measures

PrimaryDisease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation

Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (\>25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by

Time frame:
From cycle one Day 1 of the treatment through the end of treatment, up to 64 weeks
Reported as:
Mean · Proportion of participants
Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation
Proportion of participantsCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation0.219 ± 0.0480.379 ± 0.09—
PrimaryDisease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With a 95% Confidence Interval

Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (i.e., \>25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by

Time frame:
From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks
Reported as:
Number · percentage of participants
Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With a 95% Confidence Interval
percentage of participantsCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With a 95% Confidence Interval21.9 (13.1 to 33.1)37.9 (20.7 to 57.7)—
PrimaryProgression Free Survival (PFS)

PFS is defined as the date of on-study to the date of disease progression or death, estimated with the Kaplan-Meier method and reported with a 95% confidence interval. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is \>25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids.

Time frame:
From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks
Reported as:
Median · Days
Progression Free Survival (PFS)
DaysCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Progression Free Survival (PFS)56.5 (55 to 111)133 (110 to 223)—
PrimaryProgression Free Survival at 6 Months With 95% Confidence Interval

PFS-6 is the rate of durable Stable Disease lasting at least 6 months defined from the day of study entry until imaging is confirmed to show disease progression reported with a 95% confidence interval based on the Brookmeyer-Crowley method. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is \>25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable or increasing doses of corticosteroids.

Time frame:
6 months after the initiation of treatment, up to 24 weeks
Reported as:
Median · Percentage of participants
Progression Free Survival at 6 Months With 95% Confidence Interval
Percentage of participantsCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Progression Free Survival at 6 Months With 95% Confidence Interval21.9 (13.1 to 33.1)37.9 (20.7 to 57.7)—
SecondaryOverall Survival (OS)

OS is defined as the date of on-study to the date of death from any cause or last follow up, estimated with the Kaplan-Meier method and reported with a 95% confidence interval based on the Brookmeyer-Crowley method.

Time frame:
Time from the study entry and after initiation of nivolumab to participants death, up to 5 years
Reported as:
Median · years
Overall Survival (OS)
yearsCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Overall Survival (OS)1.62 (1.05 to 3.42)3.47 (2.15 to NA)—
SecondaryMean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With a 95% Confidence Interval, at Each Time Point

Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference.

Time frame:
Baseline (Up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)
Reported as:
Mean · score on a scale
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With a 95% Confidence Interval, at Each Time Point
score on a scaleCohort 1- Heavily Pre-Treated: Symptom SeverityCohort 1- Heavily Pre-Treated: Symptom InterferenceCohort 2 - Non-Heavily Pre-Treated: Symptom SeverityCohort 2 - Non-Heavily Pre-Treated: Symptom InterferenceParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Baseline (Up to 14 days prior to treatment)1.94 (1.53 to 2.34)2.92 (2.31 to 3.54)2.06 (1.145 to 2.68)3.63 (2.51 to 4.75)—
Cycle 22.16 (1.66 to 2.65)2.89 (2.12 to 3.66)1.50 (1.10 to 1.90)2.38 (1.28 to 3.47)—
Cycle 42.04 (1.52 to 2.56)3.25 (2.3 to 4.2)1.50 (0.86 to 2.13)2.87 (1.36 to 4.39)—
Cycle 61.36 (0.96 to 1.77)1.52 (0.82 to 2.22)0.88 (0.30 to 1.46)1.17 (0.11 to 2.23)—
Cycle 81.36 (0.86 to 1.86)1.3 (0.57 to 2.04)1.14 (0.38 to 1.91)1.78 (0.40 to 3.16)—
Cycle 101.39 (0.46 to 2.33)2.19 (0.68 to 3.71)0.96 (-0.04 to 1.97)1.03 (0.17 to 1.90)—
Cycle 120.88 (0.15 to 1.61)1.47 (0.40 to 2.53)0.72 (0.18 to 1.25)1.3 (-0.09 to 2.69)—
SecondaryMean Symptom Burden Severity & Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) & MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With Standard Deviation(SD) at Each Time Point

Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference.

Time frame:
Baseline (up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, or 12 (one cycle = 4 weeks)
Reported as:
Mean · score on a scale
Mean Symptom Burden Severity & Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) & MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With Standard Deviation(SD) at Each Time Point
score on a scaleCohort 1- Heavily Pre-Treated: Symptom SeverityCohort 1- Heavily Pre-Treated: Symptom InterferenceCohort 2 - Non-Heavily Pre-Treated: Symptom SeverityCohort 2 - Non-Heavily Pre-Treated: Symptom InterferenceParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Baseline (up to 14 days prior to treatment)1.94 ± 1.802.92 ± 2.722.06 ± 1.593.63 ± 2.91—
Cycle 22.16 ± 1.792.89 ± 2.811.50 ± 1.002.38 ± 2.73—
Cycle 42.04 ± 1.393.25 ± 2.521.50 ± 1.302.87 ± 3.09—
Cycle 61.36 ± 0.721.52 ± 1.230.88 ± 0.981.17 ± 1.79—
Cycle 81.36 ± 0.761.3 ± 1.131.14 ± 1.171.78 ± 2.11—
Cycle 101.39 ± 1.062.19 ± 1.730.96 ± 1.141.03 ± 0.99—
Cycle 120.88 ± 0.741.47 ± 1.090.72 ± 0.611.3 ± 1.58—
SecondaryMean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With 95% Confidence Interval

Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Higher scores indicate. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Response status was determined by whether disease progression occurred prior to or at cycle 6 or not. Participants who had disease progression prior to or at cycle 6 were non-responders and participants who did not have disease progression by cycle 6 were responders. Relevant MDASI-BT \& MDASI-SP data are those that correspond to the cycle where response status was determined. It is a unique cycle for each participant.

Time frame:
Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.
Reported as:
Mean · score on a scale
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With 95% Confidence Interval
score on a scaleCohort 1- Heavily Pre-Treated: RespondersCohort 1- Heavily Pre-Treated: Non-RespondersCohort 2 - Non-Heavily Pre-Treated: RespondersCohort 2 - Non-Heavily Pre-Treated: Non-RespondersParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Symptom severity1.61 (0.86 to 2.36)2.19 (1.74 to 2.64)1.08 (0.45 to 1.70)1.91 (1.22 to 2.61)—
Symptom interference2.12 (1.04 to 3.20)3.19 (2.49 to 3.90)1.68 (0.32 to 3.03)3.39 (1.96 to 4.82)—
Statistical analysis
  • Cohort 1- Heavily Pre-Treated: Responders vs Cohort 1- Heavily Pre-Treated: Non-Responders · Two-sample t-test · p = 0.18 (The reported p-value is representative of the mean difference in symptom severity between responders and non-responders in Cohort 1.)
  • Cohort 2 - Non-Heavily Pre-Treated: Responders vs Cohort 2 - Non-Heavily Pre-Treated: Non-Responders · Two-sample t-test · p = 0.11 (The reported p-value is representative of the mean difference in symptom severity between responders and non-responders in Cohort 2.)
  • Cohort 1- Heavily Pre-Treated: Responders vs Cohort 1- Heavily Pre-Treated: Non-Responders · Two-sample t-test · p = 0.16 (The reported p-value is representative of the mean difference in symptom interference between responders and non-responders in Cohort 1.)
  • Cohort 2 - Non-Heavily Pre-Treated: Responders vs Cohort 2 - Non-Heavily Pre-Treated: Non-Responders · Two-sample t-test · p = 0.09 (The reported p-value is representative of the mean difference in symptom interference between responders and non-responders in Cohort 2.)
SecondaryMean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With Standard Deviation

Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Higher scores indicate. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Response status was determined by whether disease progression occurred prior to or at cycle 6 or not. Participants who had disease progression prior to or at cycle 6 were non-responders and participants who did not have disease progression by cycle 6 were responders. Relevant MDASI-BT \& MDASI-SP data are those that correspond to the cycle where response status was determined. It is a unique cycle for each participant.

Time frame:
Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.
Reported as:
Mean · score on a scale
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With Standard Deviation
score on a scaleCohort 1- Heavily Pre-Treated RespondersCohort 1- Heavily Pre-Treated Non-RespondersCohort 2 - Non-Heavily Pre-Treated RespondersCohort 2 - Non-Heavily Pre-Treated Non-RespondersParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Symptom severity1.61 ± 1.102.19 ± 1.741.08 ± 0.961.91 ± 1.33—
Symptom interference2.12 ± 1.863.19 ± 2.541.68 ± 1.773.39 ± 2.78—
Statistical analysis
  • Cohort 1- Heavily Pre-Treated Responders vs Cohort 1- Heavily Pre-Treated Non-Responders · Two-sample t-test · p = 0.18The reported two-sample t-test is representative of the mean difference in symptom severity between responders and non-responders in Cohort 1.
  • Cohort 2 - Non-Heavily Pre-Treated Responders vs Cohort 2 - Non-Heavily Pre-Treated Non-Responders · Two-sample t-test · p = 0.11The reported two-sample t-test is representative of the mean difference in symptom severity between responders and non-responders in Cohort 2.
  • Cohort 1- Heavily Pre-Treated Responders vs Cohort 1- Heavily Pre-Treated Non-Responders · Two-sample t-test · p = 0.16The reported two-sample t-test is representative of the mean difference in symptom interference between responders and non-responders in Cohort 1.
  • Cohort 2 - Non-Heavily Pre-Treated Responders vs Cohort 2 - Non-Heavily Pre-Treated Non-Responders · Two-sample t-test · p = 0.09The reported two-sample t-test is representative of the mean difference in symptom interference between responders and non-responders in Cohort 2.
SecondaryMean Change Scores in Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Between Baseline and Even-numbered Cycle

Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Mean change score is even-numbered cycle minus baseline. Hence, negative change scores indicate improvement.

Time frame:
Between Baseline (up to 14 days prior to treatment) and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)
Reported as:
Mean · score on a scale
Mean Change Scores in Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Between Baseline and Even-numbered Cycle
score on a scaleCohort 1- Heavily Pre-Treated: Symptom SeverityCohort 1- Heavily Pre-Treated: Symptom InterferenceCohort 2 - Non-Heavily Pre-Treated: Symptom SeverityCohort 2 - Non-Heavily Pre-Treated: Symptom InterferenceParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Baseline to Cycle 20.22 (-0.11 to 0.55)0.07 (-0.51 to 0.64)-0.37 (-0.79 to 0.05)-1.14 (-2.28 to -0.01)—
Baseline to Cycle 40.34 (-0.14 to 0.83)0.76 (-0.20 to 1.72)-0.06 (-0.67 to 0.54)0.06 (-1.50 to 1.63)—
Baseline to Cycle 60.08 (-0.21 to 0.38)-0.52 (-1.61 to 0.57)-0.41 (-0.81 to -0.02)-1.56 (-2.91 to -0.21)—
Baseline to Cycle 80.11 (-0.37 to 0.59)-0.56 (-1.45 to 0.32)-0.26 (-0.89 to 0.36)-1.06 (-2.24 to 0.13)—
Baseline to Cycle 10-0.07 (-0.64 to 0.49)-0.12 (-1.25 to 1.01)-0.15 (-1.25 to 0.96)-1.93 (-4.24 to 0.37)—
Baseline to Cycle 12-0.44 (-1.14 to 0.26)-0.33 (-1.65 to 0.98)-0.39 (-1.0 to 0.21)-1.67 (-4.16 to 0.82)—
Statistical analysis
  • Cohort 1- Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.36The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 2 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.23The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 4 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.54The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 6 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.69The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 8 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.80The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 10 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.23The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 12 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.83The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 2 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.13The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 4 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.37The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 6 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.25The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 8 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.85The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 10 in Cohort 1.
  • Cohort 1- Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.65The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 12 in Cohort 1.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.08The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 2 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.86The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 4 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.048The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 6 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.33The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 8 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.59The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 10 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Severity · One-sample t-test · p = 0.15The reported one-sample t-test is representative of the change in mean severity between baseline and cycle 12 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.061The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 2 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.94The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 4 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.047The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 6 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.12The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 8 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.18The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 10 in Cohort 2.
  • Cohort 2 - Non-Heavily Pre-Treated: Symptom Interference · One-sample t-test · p = 0.26The reported one-sample t-test is representative of the change in mean interference between baseline and cycle 12 in Cohort 2.
SecondaryNumber of Grades 1, 2, 3, 4, and/or 5 Treatment Related Serious and/or Non-serious Adverse Events and Type

Here is the number of Grade 1, 2, 3, 4, and/or 5 serious and/or non-serious adverse events and type assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Time frame:
Adverse Events were monitored/assessed from the first study intervention, Study Day 1 through 100 days after the study agent was last administered, up to 5 years
Reported as:
Number · adverse events
Number of Grades 1, 2, 3, 4, and/or 5 Treatment Related Serious and/or Non-serious Adverse Events and Type
adverse eventsCohort 1- Heavily Pre-Treated: Grade 1Cohort 1- Heavily Pre-Treated: Grade 2Cohort 1- Heavily Pre-Treated: Grade 3Cohort 1- Heavily Pre-Treated: Grade 4Cohort 1- Heavily Pre-Treated: Grade 5Cohort 2 - Non-Heavily Pre-Treated: Grade 1Cohort 2 - Non-Heavily Pre-Treated: Grade 2Cohort 2 - Non-Heavily Pre-Treated: Grade 3Cohort 2 - Non-Heavily Pre-Treated: Grade 4Cohort 2 - Non-Heavily Pre-Treated: Grade 5Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Non-Serious - Abdominal pain1300020000—
Non-Serious - Abducens nerve disorder1000000000—
Non-Serious - Adrenal insufficiency6000050000—
Non-Serious - Agitation0200010000—
Non-Serious - Alanine aminotransferase increased10400041100—
Non-Serious - Alkaline phosphatase increased9000020000—
Non-Serious - Allergic rhinitis1000000000—
Non-Serious - Alopecia2100010000—
Non-Serious - Anal hemorrhage1000000000—
Non-Serious - Anemia131040052100—
Non-Serious - Anorexia2200000000—
Non-Serious - Anxiety1300030000—
Non-Serious - Arthralgia6000030000—
Non-Serious - Aspartate aminotransferase increased10210030000—
Non-Serious - Ataxia0100010000—
Non-Serious - Back pain4400042000—
Non-Serious - Blood bilirubin increased0000010000—
Non-Serious - Blood lactate dehydrogenase increased0000030000—
Non-Serious - Blurred vision2400011000—
Non-Serious - Cardiac disorders - Other, specify: Chest heaviness0000010000—
Non-Serious - Chest pain - cardiac0000010000—
Non-Serious - Chills1000000000—
Non-Serious - Cholesterol high1000000000—
Non-Serious - Concentration impairment1000000000—
Non-Serious - Confusion2000050000—
Non-Serious - Conjunctivitis0000010000—
Non-Serious - Constipation9400031000—
Non-Serious - Cough5400010000—
Non-Serious - Creatinine increased2000061000—
Non-Serious - Depressed level of consciousness1010000000—
Non-Serious - Depression1000010000—
Non-Serious - Diarrhea113000104000—
Non-Serious - Dizziness3100041000—
Non-Serious - Dry mouth3000010000—
Non-Serious - Dry skin1000020000—
Non-Serious - Dysesthesia1000001000—
Non-Serious - Dysphagia1200010000—
Non-Serious - Dysphasia2300010000—
Non-Serious - Dyspnea2100020000—
Non-Serious - Dysuria1000000000—
Non-Serious - Ear and labyrinth disorders - Other, specify: Hearing Issues1000000000—
Non-Serious - Edema limbs5000040000—
Non-Serious - Epistaxis0100010000—
Non-Serious - Eye disorders - Other, specify: Left eye redness1000000000—
Non-Serious - Eye disorders - Other, specify: Right homonymous hemianopsia1000001000—
Non-Serious - Eye disorders - Other, specify: Subconjunctival hemorrhage0000010000—
Non-Serious - Eye disorders - Other, specify: eyes are swelling0000010000—
Non-Serious - Facial muscle weakness0000010000—
Non-Serious - Facial nerve disorder1000000000—
Non-Serious - Facial pain1000001000—
Non-Serious - Fall14500081000—
Non-Serious - Fatigue1910100134100—
Non-Serious - Fever6100020000—
Non-Serious - Flank pain1000000000—
Non-Serious - Floaters1000010000—
Non-Serious - Flushing2000000000—
Non-Serious - Fracture1200000100—
Non-Serious - Gait disturbance5530054300—
Non-Serious - Gastrointestinal disorders - Other, specify: Gastrointestinal virus0000010000—
Non-Serious - Gastrointestinal pain0000010000—
Non-Serious - General disorders and administration site conditions - Other, specify: Joint pain1100000000—
Non-Serious - Generalized muscle weakness2210020100—
Non-Serious - Headache17910084000—
Non-Serious - Hearing impaired2100010000—
Non-Serious - Hematoma1000000000—
Non-Serious - Hemoglobin increased0000010000—
Non-Serious - Hepatobiliary disorders - Other, specify: Cholelithiasis1000000000—
Non-Serious - Hiccups1200000000—
Non-Serious - Hoarseness1000000000—
Non-Serious - Hot flashes0000010000—
Non-Serious - Hypercalcemia0000010000—
Non-Serious - Hyperglycemia122000100000—
Non-Serious - Hyperkalemia1100000000—
Non-Serious - Hypernatremia1000000000—
Non-Serious - Hypertension96300116000—
Non-Serious - Hyperthyroidism7000021000—
Non-Serious - Hypertriglyceridemia1000000000—
Non-Serious - Hypocalcemia1000000000—
Non-Serious - Hypoglycemia1000000000—
Non-Serious - Hypokalemia4100000000—
Non-Serious - Hyponatremia21000100100—
Non-Serious - Hypophosphatemia1000010000—
Non-Serious - Hypotension1000020200—
Non-Serious - Hypothyroidism5200061000—
Non-Serious - Infections and infestations - Other, specify: COVID1000000000—
Non-Serious - Infections and infestations - Other, specify:COVID-191000001000—
Non-Serious - Infections and infestations - Other, specify: RSV positive1000000000—
Non-Serious - Infections and infestations - Other, specify: Right ear infection0000010000—
Non-Serious - Infections and infestations - Other, specify: Hidradenitis suppurative in groin area0000010000—
Non-Serious - Infections and infestations - Other, specify: positive for COVID-191100000000—
Non-Serious - Insomnia8000070000—
Non-Serious - Investigations - Other, specify: Creatinine1100000000—
Non-Serious - Investigations - Other, specify: Increased TSH1000000000—
Non-Serious - Investigations - Other, specify: Thyroid stimulating hormone increased4000010000—
Non-Serious - Irregular menstruation0000010000—
Non-Serious - Irritability1000000000—
Non-Serious - Lethargy1100000000—
Non-Serious - Localized edema1000000000—
Non-Serious - Lymphocyte count decreased2518800144100—
Non-Serious - Malaise1000010000—
Non-Serious - Memory impairment1000010000—
Non-Serious - Metabolism and nutrition disorders - Other, specify: diabetic ketoacidosis1000000000—
Non-Serious - Mucositis oral1200000000—
Non-Serious - Muscle cramp1000010000—
Non-Serious - Muscle weakness left-sided1200001000—
Non-Serious - Muscle weakness lower-limb2500012000—
Non-Serious Muscle weakness right-sided2000000000—
Non-Serious Muscle weakness upper limb0100012000—
Non-Serious Musculoskeletal and connective tissue disorder - Other, specify: Muscle cramp/spasm1000010000—
Non-Serious Myalgia0100010000—
Non-Serious Nausea11600020000—
Non-Serious Neck pain1000021000—
Non-Serious Neoplasms benign, malignant&unspecified Bx Parotid lesion;confirmed basal cell carcinoma0000010000—
Non-Serious Neoplasms benign, malignant and unspecified(cysts&polyps) Epidermal Inclusion Cyst (EIC)1000000000—
Non-Serious Neoplasms benign, malignant & unspecified (incl cysts &polyps)Other, specify:Lung Nodule1000000000—
Non-Serious Nervous system disorders - Other, specify: Mild receptive aphasia10000000000—
Non-Serious Nervous system disorders - Other, specify: R hemisensory loss0000010000—
Non-Serious Nervous system disorders - Other, specify: Subtle frontal Release1000000000—
Non-Serious Nervous system disorders - Other, specify: dysesthesia1000000000—
Non-Serious Neutrophil count decreased71020010000—
Non-Serious Non-cardiac chest pain2300010000—
Non-Serious Pain18400032000—
Non-Serious Pain in extremity2300031000—
Non-Serious Paresthesia8200051000—
Non-Serious Peripheral motor neuropathy1000000000—
Non-Serious Pharyngolaryngeal pain1000000000—
Non-Serious Platelet count decreased150000071000—
Non-Serious Pruritus10100081100—
Non-Serious Rash acneiform1000010000—
Non-Serious Rash maculo-papular9310033000—
Non-Serious Renal and urinary disorders - Other, specify: Urine Odor0000010000—
Non-Serious Respiratory, thoracic and mediastinal disorders - Other, specify: Bronchiolitis0000010000—
Non-Serious Respiratory,thoracic&mediastinal disordersOther,specifySome dry throat for past~ 3weeks0000010000—
Non-Serious Seizure3300031000—
Non-Serious Sinus bradycardia3000040000—
Non-Serious Sinus tachycardia2000010000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: FACE, INTERMITTENT SINCE 19941000000000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: Face Rash0000010000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: Felt Clammy0000010000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: Left scalp lesion1000000000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: R hand rash0000010000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: On Ankles1000000000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: RASH ABD/CHEST/BACK0000011000—
Non-Serious Skin & subcutaneous tissue disorders/Other, specify:Rash, lower extremities, knees/below1000000000—
Non-Serious Skin induration0000010000—
Non-Serious Skin infection2100021000—
Non-Serious Somnolence1000011000—
Non-Serious Spasticity1010000000—
Non-Serious Thyroid stimulating hormone increased2000030000—
Non-Serious Tinnitus1000000000—
Non-Serious Tremor2000010000—
Non-Serious Urinary frequency1000010000—
Non-Serious Urinary incontinence5000010000—
Non-Serious Urinary retention0100012000—
Non-Serious Urine discoloration0000010000—
Non-Serious Ventricular arrhythmia1000000000—
Non-Serious Vertigo1000000000—
Non-Serious Voice alteration0000010000—
Non-Serious Vomiting8600000100—
Non-Serious Weight gain1100020100—
Non-Serious Weight loss1000020000—
Non-Serious White blood cell decreased231020062000—
Non-Serious Allergic reaction0100000000—
Non-Serious Aspiration0110000000—
Non-Serious Burn0000001000—
Non-Serious Buttock pain0100000000—
Non-Serious CD4 lymphocytes decreased2250050000—
Non-Serious Cataract0100000000—
Non-Serious Cognitive disturbance0000001100—
Non-Serious Colitis0100000000—
Non-Serious Dehydration0100000000—
Non-Serious Dry eye0100000000—
Non-Serious Dysarthria0100000000—
Non-Serious Ear and labyrinth disorders - Other, specify: Left ear drainage0000001100—
Non-Serious Eye disorders - Other, specify: Diplopia0100000000—
Non-Serious Eye pain0100000000—
Non-Serious Eyelid function disorder0000001000—
Non-Serious Flu like symptoms0300000000—
Non-Serious Gastroesophageal reflux disease0300000000—
Non-Serious Infections and infestations - Other, specify: FLU0100000000—
Non-Serious Infections and infestations - Other, specify: Thrush0100000000—
Non-Serious Infections and infestations - Other, specify: Urinary Tract Infection0100000000—
Non-Serious Infusion related reaction0300000000—
Non-Serious Infusion site extravasation0000001000—
Non-Serious Injury, poisoning and procedural complications - Other, specify: Incisional drainage0100000000—
Non-Serious Investigations - Other, specify: Low iron0200000000—
Non-Serious Metabolism and nutrition disorders - Other, specify: Low iron0100000000—
Non-Serious Musculoskeletal and connective tissue disorder - Other, specify: Left jaw pain0000001200—
Non-Serious Nervous system disorders - Other, specify: Facial Muscle Weakness (Left)0100000000—
Non-Serious Nervous system disorders - Other, specify: Intermittent worsening of R hemisensory loss0000001100—
Non-Serious Nervous system disorders - Other, specify: Neuropathic back pain0000001000—
Non-Serious Nervous system disorders - Other, specify: R SIDE LACK OF COORDINATION0100000000—
Non-Serious Oral pain0100000000—
Non-Serious Papilledema0100001000—
Non-Serious Peripheral sensory neuropathy0110000000—
Non-Serious Presyncope0100000000—
Non-Serious Productive cough0100000000—
Non-Serious Respiratory, thoracic and mediastinal disorders - Other, specify: Covid 190000001000—
Non-Serious Sinusitis0000001000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: Dermatitis0100000000—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: blister, right 1st toe0100000000—
Non-Serious Stroke0100000000—
Non-Serious Surgical and medical procedures - Other, specify: Scalp Revision Surgery0000001000—
Non-Serious Surgical and medical procedures - Other, specify: outpatient debridement - scalp wound0100000000—
Non-Serious Thromboembolic event0000001100—
Non-Serious Upper respiratory infection0100000000—
Non-Serious Urinary tract infection01010003000—
Non-Serious Urinary urgency0100000000—
Non-Serious Vestibular disorder0100000000—
Non-Serious Wound dehiscence0000001000—
Non-Serious Intracranial hemorrhage0110000000—
Non-Serious Urinary tract obstruction0010000000—
Serious Seizure1030001000—
Serious Vomiting1200000000—
Serious Anemia0100000000—
Serious Blurred vision0100000000—
Serious Chest pain - cardiac0000001000—
Serious Cognitive disturbance0100000000—
Serious Colitis0000001100—
Serious Flu-like symptoms0110000000—
Serious Generalized muscle weakness0000001000—
Serious Headache0130000000—
Serious Intracranial hemorrhage0111000010—
Serious Myocardial infarction0000001000—
Serious Nausea0100000000—
Serious Tumor hemorrhage0100000000—
Serious Urinary incontinence0000001000—
Serious Urinary tract infection0110000000—
Serious Alanine aminotransferase increased0010000000—
Serious Appendicitis perforated0010000000—
Serious Confusion0010000000—
Serious Dehydration0000000100—
Serious Dysphagia0010000000—
Serious Edema cerebral0003000100—
Serious Encephalopathy0010000000—
Serious Eye disorders - Other, specify: vision decreased0010000000—
Serious Facial pain0000000100—
Serious Fall0000000100—
Serious Fatigue0010000000—
Serious Fracture0020000000—
Serious Gastrointestinal disorders - Other, specify: perforated cecum0000000100—
Serious General disorders and administration site conditions - Other, specify: Aphasia0010000000—
Serious General disorders and administration site conditions - Other, specify: Disease Progression00100000300—
Serious General disorders and administration site conditions - Other, specify: Encephalopathy0010000000—
Serious General disorders &administration site conditions - Other, specify: Treatment effect/changes0010000000—
Serious Hematoma0000000100—
Serious Hydrocephalus0031000000—
Serious Hyperglycemia0010000000—
Serious Infections and infestations - Other, specify: GI VIRAL INFECTION0010000000—
Serious Metabolism and nutrition disorders - Other, specify: Failure to thrive0010000000—
Serious Muscle weakness lower limb0000000100—
Serious Neoplasms benign,malignant&unspecified(incl cysts & polyps)-Prominent lymphocytic infiltrate0010000000—
Serious Neoplasms benign,malignant&unspecified (incl cysts&polyps)-Tumor debulking (tumor resection)0000000100—
Serious Pain0000000100—
Serious Paresthesia0010000100—
Serious Respiratory, thoracic and mediastinal disorders -Other, specify: Immune mediated pneumonitis0010000000—
Serious Skin infection0010000000—
Serious Surgical and medical procedures - Other, specify: Craniotomy0010000000—
Serious Surgical and medical procedures - Other, specify: Incisional drainage0010000000—
Serious Surgical and medical procedures - Other, specify: Laminectomy0000000200—
Serious Surgical and medical procedures - Other, specify: Resection-Parotid gland tumor0010000000—
Serious Surgical and medical procedures - Other, specify: Tumor resection0010000000—
Serious Surgical and medical procedures - Other, specify: surgical resection0010000000—
Serious Thromboembolic event0000000200—
Serious Tumor pain0010000000—
Serious Wound dehiscence0000000200—
Serious Infections and infestations - Other, specify: Aspiration Pneumonia0001000000—
Serious Platelet count decreased0001000000—
Serious Sepsis0001000001—
Serious Injury, poisoning and procedural complications - Other, specify: Posterior Fossa Hemorrhage0000100000—
Serious Lung infection0000100200—
Serious Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify: ATRT0000100000—
Serious Neoplasms benign,malignant &unspecified(incl cysts&polyps)- Atypical Teratoid Rhabdoid Tumor0000100000—
Serious Neoplasms benign, malignant & unspecified (incl cysts & polyps)Other: Diffuse midline glioma0000100000—
Serious Neoplasms benign, malignant&unspecified (incl cysts&polyps)Other,specify:Disease progression0000100000—
Serious Neoplasms benign, malignant & unspecified (incl cysts & polyps) -Other, specify: Gliosarcoma0000000001—
Serious Neoplasms benign, malignant & unspecified (incl cysts &polyps) - Other, MALIGNANT MENINGIOMA0000100000—
Serious Neoplasms benign, malignant&unspecified (incl cysts&polyps) - Other, specify:MEDULLOBLASTOMA0000100000—
Serious Neoplasms benign, malignant & unspecified (incl cysts&polyps) -Other, specify:MIDLINE GLIOMA0000100000—
Serious Neoplasms benign,malignant&unspecified (incl cysts&polyps)Other:PAPILLARY TUMOR PINEAL GLAND0000100000—
Serious Neoplasms benign, malignant&unspecified (incl cysts/polyps)Other,specify:PROGRESSIVE DISEASE0000100001—
Non-Serious Eye Disorders - Other, specify: Central Retinal Vein Occlusion - Left Eye0000001000—
Non-Serious Injury, poisoning and procedural complications - Other, specify: Bee sting0100000000—
Non-Serious Nasal congestion0100000000—
Non-Serious Thrush0100000000—
Non-Serious Edema cerebral0010000000—
Non-Serious Hydrocephalus0010000000—
Non-Serious Hypoxia0000000100—
Non-Serious Eye Disorders - Other, Specify: Hemianopsias (LEFT)0010000000—
Non-Serious Nervous System Disorders - Other, specify: Neuropathic abdominal pain0000000100—
Non-Serious Musculoskeletal and connective tissue disorder - Other, specify: muscle spasm/cramp1000000000—
Non-Serious Ear pain0000000100—
Non-Serious Skin and subcutaneous tissue disorders - Other, specify: Rash papular1010000000—
Non-Serious - Investigations - Other, specify:Thyroid stimulating hormone increased0000010000—
Other pre-specifiedNumber of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame:
Adverse Events were monitored/assessed from the first study intervention, Study Day 1 through 100 days after the study agent was last administered, up to 5 years
Reported as:
Count of participants · Participants
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
ParticipantsCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).7630—

Adverse events

Collected over All-Cause Mortality was monitored/documented throughout the study and up to 5 years post treatment &/or until early termination of the study. Document adverse events from the first study intervention, Study Day 1 through 100 days after the study agent was last administered. Adverse events that are serious need to be recorded in 100 days. Beyond 100 days after the last intervention, only adverse events which are serious and related to the study intervention need to be recorded for up to 5 years.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1- Heavily Pre-Treated42/76 (55.3%)43/76 (56.6%)70/76 (92.1%)
Cohort 2 - Non-Heavily Pre-Treated10/30 (33.3%)13/30 (43.3%)29/30 (96.7%)
Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles1/30 (3.3%)0/30 (0%)0/30 (0%)
Most frequent serious events
Showing 10 of 67
Most frequent serious events
EventCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
General disorders and administration site conditions - Other, specify: Disease ProgressionGeneral disorders10/763/30—
ColitisGastrointestinal disorders0/762/30—
Surgical and medical procedures - Other, specify: LaminectomySurgical and medical procedures0/762/30—
Thromboembolic eventVascular disorders0/762/30—
HeadacheNervous system disorders4/760/30—
HydrocephalusNervous system disorders4/760/30—
SeizureNervous system disorders4/761/30—
Edema cerebralNervous system disorders3/761/30—
Intracranial hemorrhageNervous system disorders3/761/30—
VomitingGastrointestinal disorders3/760/30—
Most frequent other events
Showing 10 of 221
Most frequent other events
EventCohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment Cycles
FatigueGeneral disorders27/7616/30—
Lymphocyte count decreasedInvestigations21/7610/30—
HeadacheNervous system disorders22/769/30—
DiarrheaGastrointestinal disorders11/768/30—
HyperglycemiaMetabolism and nutrition disorders11/768/30—
HypertensionVascular disorders5/768/30—
PruritusSkin and subcutaneous tissue disorders9/768/30—
Gait disturbanceGeneral disorders11/767/30—
FallInjury, poisoning and procedural complications13/766/30—
HypothyroidismEndocrine disorders6/766/30—

Baseline characteristics

All participants enrolled who have baseline data are reported.

Age, Categorical
Age, Categorical(Participants)Cohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment CyclesTotal
<=18 years0000
Between 18 and 65 years652324112
>=65 years117624
Age, Continuous
Age, Continuous(years)Cohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment CyclesTotal
Mean47.42 ± 15.9353.07 ± 17.0149.77 ± 16.1549.18 ± 16.26
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment CyclesTotal
Female3791460
Male39211676
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment CyclesTotal
Hispanic or Latino164222
Not Hispanic or Latino592528112
Unknown or Not Reported1102
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment CyclesTotal
American Indian or Alaska Native1102
Asian5128
Native Hawaiian or Other Pacific Islander0101
Black or African American5139
White602324107
More than one race1012
Unknown or Not Reported4307
Region of Enrollment
Region of Enrollment(participants)Cohort 1- Heavily Pre-TreatedCohort 2 - Non-Heavily Pre-TreatedParticipants Enrolled Who Were Not Treated OR Completed Treatment CyclesTotal
United States763030136
08

Study locations

3 sites
  • Northwestern University
    Chicago, Illinois 60611, United States
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
  • UT MD Anderson Cancer Center
    Houston, Texas 77030-4096, United States
09

References and documents

Publications

  • Gilbert MR, Ruda R, Soffietti R. Ependymomas in adults. Curr Neurol Neurosci Rep. 2010 May;10(3):240-7. doi: 10.1007/s11910-010-0109-3. PubMed 20425040 ↗
  • Okada H, Weller M, Huang R, Finocchiaro G, Gilbert MR, Wick W, Ellingson BM, Hashimoto N, Pollack IF, Brandes AA, Franceschi E, Herold-Mende C, Nayak L, Panigrahy A, Pope WB, Prins R, Sampson JH, Wen PY, Reardon DA. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015 Nov;16(15):e534-e542. doi: 10.1016/S1470-2045(15)00088-1. PubMed 26545842 ↗
  • Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, Algazi AP, Pampaloni MH, Lobach IV, Hwang J, Pierce RH, Gratz IK, Krummel MF, Rosenblum MD. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016 Sep 1;126(9):3447-52. doi: 10.1172/JCI87324. Epub 2016 Aug 15. PubMed 27525433 ↗
  • Collins RRJ, Florke Gee RR, Tozandehjani S, Bayat T, Hoyos Sanchez MC, Gutierrez JSS, Breznik B, Lee AK, Peters ST, Connelly JP, Pruett-Miller SM, Roussel MF, Rakheja D, Tillman HS, Potts PR, Fon Tacer K. Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors. Acta Neuropathol Commun. 2025 Jul 28;13(1):164. doi: 10.1186/s40478-025-02055-3. PubMed 40721826 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

Time frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.

Access criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

10

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jul 2017 to primary completion in Jun 2025, 95 months.

Results were first posted in Aug 2026, 1 year 1 month after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
May 31, 2017
First posted
Jun 2, 2017
StartActual
Jul 13, 2017
Primary completionActual
Jun 23, 2025
CompletionActual
Jun 23, 2025
Results first posted
Aug 18, 2026
Last update
Oct 27, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Results
Posted results revised
revised Oct 27, 2026
Documents
Oct 27, 2026
Show all 1 update
  1. Oct 27, 2026
    Posted results revised
    Documents Protocol and statistical analysis plan ↗ updated
    + 3 other changes: verification date, responsible party and contact details

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT03173950
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Kevin Camphausen, M.D. (Principal Investigator, National Cancer Institute (NCI)) — Principal investigator
First posted
Jun 2, 2017
Start date
Jul 13, 2017
Primary completion
Jun 23, 2025
Completion
Jun 23, 2025
Results posted
Aug 18, 2026
Last update
Oct 27, 2026

Study contacts

Kevin Camphausen, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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