A Phase 1 interventional study of Actinium Ac 225 Lintuzumab and Biospecimen Collection in Recurrent Glioblastoma, IDH-Wildtype, Recurrent Gliosarcoma and Recurrent WHO Grade 4 Glioma, sponsored by National Cancer Institute (NCI). Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-12.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase I trial studies the side effects and best dose of Actimab-A when given together with cemiplimab (REGN2810) in treating patients with glioblastomas that have come back after a period of improvement (recurrent). Actimab-A consists of the monoclonal antibody lintuzumab combined with the radioactive drug actinium Ac 225. Lintuzumab specifically binds to the cell surface antigen CD33 which is found on the glioblastoma cells and delivers the actinium Ac 225. This may allow the glioblastoma to be found and treated by Actimab-A. Immunotherapy with monoclonal antibodies, such as cemiplimab (REGN2810), may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving Actimab-A with cemiplimab (REGN2810) may be safe, tolerable and/or effective in treating recurrent glioblastoma.
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of actinium Ac 225 lintuzumab (Actimab-A) in combination with cemiplimab (REGN2810) in recurrent glioblastoma.
SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity. II. To evaluate the impact of baseline tumor mutational burden on response. III. To evaluate the pharmacokinetics of cemiplimab (REGN2810). IV. To evaluate the alpha radiation dosimetry of Actimab-A.
EXPLORATORY OBJECTIVES:
I. To evaluate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) as a predictor for treatment response.
II. To evaluate the impact of baseline tumor expression signatures on response. III. To evaluate the correlation of changes in cytokine production and arginase activity with response.
IV. To evaluate the impact of combination treatment on peripheral immune cells. V. To correlate adverse events (AEs) with absorbed doses of radiation to organs at risk (OARs) such as the kidneys.
OUTLINE: This is a dose-escalation study of Actimab-A in combination with cemiplimab.
Patients receive Actimab-A intravenously (IV) over 30 minutes on either days 1 and 22 of cycles 1-3, days 1 and 22 of cycles 1 and 2, or days 1 and 22 of cycle 1 and day 1 of cycle 2. Patients also receive cemiplimab IV over 30 minutes on days 1 and 22 of each cycle. Cycles repeat every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and radiologic imaging throughout the study and positron emission tomography (PET)/computed tomography (CT) on study. Patients may also optionally undergo single-photon emission computed tomography (SPECT)/CT on study.
After completion of study treatment, patients are followed up at 3 weeks, 30 days, and then every 3 months for up to 2 years.
2,132 studies on the registry are indexed under Glioblastoma; 464 are open to participants now.
This study's planned enrollment of 30 is below the median of 36 across 1,753 interventional studies indexed under Glioblastoma.
Browse Glioblastoma studies →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.
Counted across the registry records on this site, refreshed daily.
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.
Patients must have or cytologically confirmed glioblastoma isocitrate dehydrogenase wild type (IDH-WT) World Health Organization (WHO) grade 4 inclusive of gliosarcoma (Louis et al., 2021)
Previous treatment with at least radiotherapy (prior dose ≥ 40 gray [Gy])
Exclusion Criteria:
Treatment with systemic medication (including, but not limited to, , cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha [TNF-α] agents) within two (2) weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
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.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
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.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
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.
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.
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.
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).
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.
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.
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.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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.
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.
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.
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.
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.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
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.
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.
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.
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.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
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.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive Actimab-A IV over 30 minutes on either days 1 and 22 of cycles 1-3, days 1 and 22 of cycles 1 and 2, or days 1 and 22 of cycle 1 and day 1 of cycle 2. Patients also receive cemiplimab IV over 30 minutes on days 1 and 22 of each cycle. Cycles repeat every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and radiologic imaging throughout the study and PET/CT on study. Patients may also optionally undergo SPECT/CT on study.
Radiation: Actinium Ac 225 Lintuzumab · Procedure: Biospecimen Collection · Biological: Cemiplimab · Procedure: Computed Tomography · Procedure: Positron Emission Tomography · Procedure: Radiologic Imaging Procedure · Procedure: Single Photon Emission Computed Tomography
Given IV
Also known as: 225Ac-HuM195, Actimab-A, Actinium (225Ac) Lintuzumab Satetraxetan, Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195, LINTUZUMAB SATETRAXETAN AC-225, SGN-33 AC-225
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Given IV
Also known as: Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN 2810, REGN-2810, REGN2810
Undergo PET/CT and/or SPECT/CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography
Undergo PET/CT
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
Undergo radiologic imaging
Undergo SPECT/CT
Also known as: Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography, SPECT, SPECT imaging, SPECT SCAN, SPET, ST, tomography, emission computed, single photon, Tomography, Emission-Computed, Single-Photon
Dose limiting toxicities (DLTs)
DLT is defined as any grade ≥ 3 non-hematologic toxicity regardless of supportive care or grade ≥ 4 hematologic toxicity per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 that occurs during the first six (6) weeks after initiating treatment. DLTs per CTCAE version 5.0 will be tabulated for each dose level.
Time frame: Up 6 weeks after initiating treatment
Maximum tolerated dose (MTD)
Will use a Bayesian optimal interval design to find the MTD. Recommended phase 2 dose determination will include both the DLT period for the MTD, as well as consideration of later cycle adverse events (AEs) and the overall safety profile, and available correlatives and will be determined by the study team and Cancer Therapy Evaluation Program collaborators.
Time frame: Up to 18 months
Frequency of AEs
AEs per CTCAE version 5.0 will be tabulated for each dose level.
Time frame: Up to 30 days after last dose of study drug
Objective response rate (ORR)
Treatment response will be assessed for all patients based on Response Assessment in Neuro-Oncology 2.0 (RANO 2.0) criteria: complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD). ORR is defined as the addition of CR and PR. ORR rate will be calculated by the proportion of evaluable patients with objective response (CR/PR), along with its exact 95% confidence interval (CI).
Time frame: Up to 2 years
Progression free survival
Treatment response will be assessed for all patients based on RANO 2.0 criteria: CR, PR, SD, and PD. Kaplan-Meier estimates will be provided. The corresponding median survival time (with 95% CI) will be determined.
Time frame: From randomization or initiation of treatment to the occurrence of disease progression or death, assessed up to 2 years
Overall survival
Treatment response will be assessed for all patients based on RANO 2.0 criteria: CR, PR, SD, and PD. Kaplan-Meier estimates will be provided. The corresponding median survival time (with 95% CI) will be determined.
Time frame: From date of diagnosis until the patient's death from any cause, assessed up to 2 years
Tumor mutational burden (TMB) (whole exome sequencing [somatic])
Will evaluate the impact of baseline TMB on response. TMB will be evaluated in each patient and correlation assessment will be performed with clinical activity by Spearman's correlation coefficient. Will also use a logistic regression model to test the association between TMB and ORR.
Time frame: At baseline
Trough and post end of infusion concentrations of cemiplimab (REGN2810) in serum
Will evaluate the pharmacokinetics (PK) of cemiplimab (REGN2810). PK exposure values will be reported descriptively.
Time frame: At cycle (C) 1 day (D) 1, C1D22, C2D1, C2D22, C3D1, and C3D22 (Cycle = 42 days)
Absorbed dose estimates (gray) in organs of interest
Will evaluate the alpha radiation dosimetry of Actimab-A. Absorbed dose calculations will be performed following Imaging and Radiation Core guidelines and Medical Internal Radiation Dose Committee methodology, assuming a relative biologic effect of five patients for alpha particles. The absorbed dose estimates to critical organs of each patient at the various administered activity levels will be tabulated using descriptive statistics. A paired T-test, or Wilcoxon signed-rank test if the data is not normally distributed, will be used to detect differences in absorbed dose between time points.
Time frame: At 4 hours, 24, 48, and 168 hours post-actinium Ac 225 lintuzumab (Actimab-A) during C2 (Cycle = 42 days)
Change in variant allele frequencies (VAF) of tumor mutations in circulating tumor deoxyribonucleic acid (ctDNA)
Will evaluate ctDNA as a predictor for treatment response. The detectable VAFs will be assessed and trended during the course of treatment. VAF change will be assessed categorically for each patient (increased or decreased at start of C3 as compared to baseline). The association of VAF change with objective response will be tested using the Fisher's exact test, where p \< 0.05 will be considered statistically significant.
Time frame: Baseline to C3 (Cycle = 42 days)
Expression of immune checkpoint receptors and myeloid derived suppressor cells markers by ribonucleic acid sequencing (RNAseq) on archival tissue
Will evaluate the impact of baseline tumor expression signatures on response. Expression levels will be evaluated in each patient and correlation assessment will be performed between T-cell density, gene response set values and other endpoints such as clinical response by Spearman's correlation coefficient.
Time frame: At C1D1, C1D8, C1D22, C2D1, C2D22, C3D1, C3D22, and progression of disease (Cycle = 42 days)
Protein expression of CD33 and PD-L1 by immunohistochemistry on archival tissue
Will evaluate the impact of baseline tumor expression signatures on response. Expression levels will be evaluated in each patient and correlation assessment will be performed with clinical response by Spearman's correlation coefficient.
Time frame: At baseline
Interferon gamma in serum by enzyme-linked immunosorbent assay (ELISA)
Will evaluate the correlation of changes in cytokine production and arginase activity with response. ELISA will quantify interferon gamma evaluated in each patient over time (paired), and between patients (non paired), from baseline to each blood draw at a significance level (alpha) of 0.05, and correlated with objective response will be tested using the Fisher's exact test, where p \< 0.05 will be considered statistically significant.
Time frame: At C1D1, C1D8, C1D22, C2D1, C2D22, C3D1, C3D22, and progression of disease (Cycle = 42 days)
Arginase activity by colorimetric assay in serum and peripheral blood mononuclear cells (PBMCs)
Will evaluate the correlation of changes in cytokine production and arginase activity with response. Arginase activity will be evaluated in each patient over time (paired), and between patients (non paired), from baseline to each blood draw with a parametric (such as t-test) or non-parametric (such as Wilcoxon signed rank / rank sum) test depending on whether the data is normally distributed at a significance level (alpha) of 0.05, and correlated with objective response will be tested using the Fisher's exact test, where p \< 0.05 will be considered statistically significant.
Time frame: At C1D1, C1D8, C1D22, C2D1, C2D22, C3D1, C3D22, and progression of disease (Cycle = 42 days)
Gene expression signatures in PBMCs
Will evaluate the impact of combination treatment on peripheral immune cells. Will include myeloid cell (polarization), T-cells (T-cell receptor \[TCR\] clonality), interferon, immunosuppression and cell cycle (RNAseq, gene set variation analysis \[GSVA\]). After correction for batch effect, GSVA scores for each gene set described will be calculated for each patient. Will assess changes within each patient over time from baseline with a parametric (such as t-test) or non-parametric (such as Wilcoxon signed rank) test depending on whether the data is normally distributed (paired within patients) at a significance level (alpha) of 0.05. Will also examine immune cell types bioinformatic deconvolution of the RNAseq data to estimate cell type frequencies. A percentage of TCR overlap of peripheral blood will be calculated and changes over time from baseline will be assessed with a parametric or non-parametric test at a significance level (alpha) of 0.05.
Time frame: At C1D1, C1D8, C1D22, C2D1, C2D22, C3D1, C3D22, and progression of disease (Cycle = 42 days)
Immune cell characterization (single cell [sc] RNAseq of PBMCs): Myeloid cell phenotypes, TCR clonality and deoxyribonucleic acid (DNA) damage
Will evaluate the impact of combination treatment on peripheral immune cells. Myeloid cell clusters, changes in unique TCR clone frequencies (and their associated phenotypes), and DNA damage and repair pathways (inclusive of cell cycle and apoptosis) will be followed through treatment and changes within each patient over time from baseline to each blood draw with a parametric (such as t-test) or non-parametric (such as Wilcoxon signed rank) test depending on whether the data is normally distributed (paired within patients) at a significance level (alpha) of 0.05. Bulb RNAseq data will be utilized to help prioritize samples to commit to scRNAseq.
Time frame: At C1D1, C1D8, C1D22, C2D1, C2D22, C3D1, C3D22, and progression of disease (Cycle = 42 days)
Immune cell characterization (flow cytometry of PBMCs): Myeloid cell phenotypes and markers of T-cell activation
Will evaluate the impact of combination treatment on peripheral immune cells. Myeloid cell phenotypes and markers of T-cell activation will be followed through treatment and changes within each patient over time from baseline to each blood draw with a parametric (such as t-test) or non-parametric (such as Wilcoxon signed rank) test depending on whether the data is normally distributed, (paired within patients) at a significance level (alpha) of 0.05.
Time frame: At C1D1, C1D8, C1D22, C2D1, C2D22, C3D1, C3D22, and progression of disease (Cycle = 42 days)
Absorbed doses of radiation to organs at risk (OARs) and severe side effects
Will explore the correlations of absorbed doses of radiation to OARs and severe side effects. For time to each toxicity event separately, will summarize using the Kaplan-Meier method. AEs will be classified into acute or late events depending on the time from re-irradiation. Univariate logistic regression models will be used to study potential associations between independent variables and toxicity. Receive-operator characteristics analysis will be performed for OAR to study the correlation between events of severe toxicity and absorbed dose. Correlations between cumulated absorbed doses by healthy organs and the variation of laboratory parameters from baseline after each treatment cycle will be assessed with the Spearman correlation coefficient. Linear mixed models will be used to estimate the variations of laboratory measurements over time as a function of the cumulative absorbed doses by organs. Statistical significance will be considered at a significance level (alpha) of 0.05.
Time frame: Up to 30 days after last dose of study drug
No study locations are listed for this record.
Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Data sharing details ↗ · grants.nih.gov
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Studies of the drug tested here: Cemiplimab
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