A Phase 1/2 interventional study of Ipilimumab and Laboratory Biomarker Analysis in Metastatic Melanoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor and Recurrent Hodgkin Lymphoma, sponsored by National Cancer Institute (NCI). Completed at 25 sites in 2 countries. Open to participants aged 12 Months to 30 Years. Per ClinicalTrials.gov, last updated 2023-10-17.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
This phase I/II trial studies the side effects and best dose of nivolumab when given with or without ipilimumab to see how well they work in treating younger patients with solid tumors or sarcomas that have come back (recurrent) or do not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better alone or with ipilimumab in treating patients with recurrent or refractory solid tumors or sarcomas.
PRIMARY OBJECTIVES:
I. Determine the tolerability, and define and describe the toxicities of nivolumab administered as a single agent in children with relapsed or refractory solid tumors at the adult recommended dose of 3 mg/kg.
II. Determine if systemic nivolumab exposure in children is similar to the systemic exposure in adults following a 3 mg/kg dose.
III. Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and define and describe the toxicities of nivolumab plus ipilimumab administered to children with relapsed or refractory solid tumors.
IV. Assess antitumor effects of nivolumab across selected childhood solid tumors in seven expansion cohorts (Parts B1-B6, B8); neuroblastoma (2 cohorts: measurable disease, metaiodobenzylguanidine [MIBG] positive only non-measurable disease), osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, and non-Hodgkin lymphoma.
V. Assess antitumor effects of nivolumab in combination with ipilimumab across selected childhood solid tumors in two dose combinations (Part D and Part E).
VI. Characterize the pharmacokinetics of nivolumab alone and in combination with ipilimumab, including area under the curve (AUC), concentration maximum (Cmax), concentration minimum (Cmin), using intensive sampling.
VII. Assess immunogenicity of nivolumab alone and in combination with ipilimumab by measuring anti-drug antibody (ADA) levels.
SECONDARY OBJECTIVES:
I. Conduct exploratory studies of the phenotypic and functional effects of nivolumab (alone and in combination with ipilimumab), as well as changes in antibodies to previously vaccinated viruses, in serum samples.
II. Explore whether correlations exist between PD-L1 expression on tumor and antitumor effects of nivolumab (alone and in combination with ipilimumab) in pediatric solid tumors and to conduct exploratory studies of potential tumor associated biomarkers of response in tumor tissue (at least five out of the following markers: NRAS, BRAF, MEK, KIT, PDGF, TP53, RB1 and BRCA1, Akt phosphorylation, IL-17 or PD-L1).
III. Explore presence of tumor infiltrating lymphocytes and their association with antitumor effects of nivolumab (alone and in combination with ipilimumab).
IV. Conduct exploratory studies of the effect of nivolumab (alone or in combination with ipilimumab) on cytokine levels in serum samples.
V. For Part E, determine tumor mutational burden of diagnostic specimens using FoundationOneCDx testing to explore immune- related gene expression or mutation and its association with antitumor response to nivolumab in combination with ipilimumab.
OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study.
PART A (COMPLETED): Patients with recurrent or refractory solid tumors receive nivolumab intravenously (IV) over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART B (COMPLETED): Patients with neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or melanoma receive nivolumab as in Part A.
PART C (COMPLETED):
INDUCTION: Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nivolumab IV as in Part A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART D (COMPLETED):
INDUCTION: Patients with neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or melanoma receive nivolumab IV and ipilimumab IV as in Part C. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART E: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at approximately 100 days, every 6 months for up to 24 months, and then annually for up to 60 months.
3,370 studies on the registry are indexed under Melanoma; 578 are open to participants now.
This study's enrollment of 140 is above the median of 40 across 2,649 interventional studies indexed under Melanoma.
Browse Melanoma 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 had histologic verification of at original diagnosis or relapse
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the defined eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
or radioisotope (GFR) >= 70 ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
Exclusion Criteria:
Patients with a history of congestive heart failure (CHF) or are at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must have adequate cardiac function as clinically indicated:
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.
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.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
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.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
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.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
See Detailed Description
Biological: Ipilimumab · Other: Laboratory Biomarker Analysis · Biological: Nivolumab · Other: Pharmacological Study
Given IV
Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy
Correlative studies
Given IV
Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Correlative studies
Frequency of Dose Limiting Toxicities of Nivolumab as a Single Agent or in Combination With Ipilimumab
The frequency (%) of patients experiencing a dose limiting toxicity at least possibly attributable to nivolumab as a single agent or in combination with ipilimumab by study part and dose level.
Time frame: 28 days
Antitumor Effect of Nivolumab as a Single Agent or in Combination With Ipilimumab
Frequency of disease response (best overall response of partial or complete response) assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR by study part and dose level.
Time frame: Up to 5 years
Pharmacodynamics of Nivolumab as a Single Agent or in Combination With Ipilimumab
Median (min,max) concentration by protein, study part, and dose level.
Time frame: Up to 28 days
Area Under the Drug Concentration Curve of Nivolumab as a Single Agent or in Combination With Ipilimumab
The median (min,max) of the area under the drug concentration curve for nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24,72,192, and 360 hours post-dose.
Time frame: Up to 15 days
Half-life of Nivolumab as a Single Agent or in Combination With Ipilimumab
The median (min,max) of the half-life of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose. The reported half-life was calculated using a linear regression of the log (concentration) versus time data for days 4, 8 and 15.
Time frame: Up to 15 days
Maximum Serum Concentration of Nivolumab as a Single Agent or in Combination With Ipilimumab
Median (min,max) of the maximum serum concentration of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose.
Time frame: Up to 15 days
Minimum Serum Concentration of Nivolumab as a Single Agent or in Combination With Ipilimumab
Median (min,max) of the minimum serum concentration of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose.
Time frame: Up to 15 days
Clearance of Nivolumab as a Single Agent or in Combination With Ipilimumab
Median (min,max) of the clearance of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose.
Time frame: Up to 15 days
PD-L1 Expression of Nivolumab as a Single Agent or in Combination With Ipilimumab
Median (min, max) of PD-L1 expression levels by study part, dose level, and disease cohort.
Time frame: Cycle 1 (21 days)
Biomarker Expression Analysis of Nivolumab as a Single Agent or in Combination With Ipilimumab
Median (min, max) expression levels by biomarker, dose level, study part, and disease cohort.
Time frame: Cycle 1 (21 days)
| Milestone | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|
| Started | 7 | 6 | 72 | 6 | 6 | 6 | 29 | 8 |
| Completed | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 7 | 6 | 71 | 6 | 6 | 6 | 29 | 8 |
| Withdrew: Adverse event | 0 | 0 | 7 | 0 | 0 | 0 | 3 | 4 |
| Withdrew: Death | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 |
| Withdrew: Lack of efficacy | 4 | 6 | 38 | 5 | 6 | 6 | 21 | 4 |
| Withdrew: Physician decision | 2 | 0 | 16 | 1 | 0 | 0 | 3 | 0 |
| Withdrew: Protocol violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 7 | 0 | 0 | 0 | 1 | 0 |
The frequency (%) of patients experiencing a dose limiting toxicity at least possibly attributable to nivolumab as a single agent or in combination with ipilimumab by study part and dose level.
| Participants | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|
| Frequency of Dose Limiting Toxicities of Nivolumab as a Single Agent or in Combination With Ipilimumab | 0 | 0 | 5 | 0 | 0 | 1 | 1 | 1 |
Frequency of disease response (best overall response of partial or complete response) assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR by study part and dose level.
| Participants | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B1: 3 mg/kg Nivolumab | Part B2: 3 mg/kg Nivolumab | Part B3: 3 mg/kg Nivolumab | Part B4: 3 mg/kg Nivolumab | Part B5: 3 mg/kg Nivolumab | Part B6: 3 mg/kg Nivolumab | Part B7: 3 mg/kg Nivolumab | Part B8: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D2: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D3: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D4: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E3: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | Part E4: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Antitumor Effect of Nivolumab as a Single Agent or in Combination With Ipilimumab | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
Median (min,max) concentration by protein, study part, and dose level.
No measurements were reported for this outcome.
The median (min,max) of the area under the drug concentration curve for nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24,72,192, and 360 hours post-dose.
| hr*ug/mL | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab |
|---|---|---|---|
| Area Under the Drug Concentration Curve of Nivolumab as a Single Agent or in Combination With Ipilimumab | 20744.5 (11840.0 to 31067.0) | 18338 (9383.0 to 31188.0) | 20816 (6442.0 to 133556.0) |
The median (min,max) of the half-life of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose. The reported half-life was calculated using a linear regression of the log (concentration) versus time data for days 4, 8 and 15.
| hours | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab |
|---|---|---|---|
| Half-life of Nivolumab as a Single Agent or in Combination With Ipilimumab | 312.5 (154.0 to 444.0) | 281.5 (263.0 to 426.0) | 379 (92.0 to 2772.0) |
Median (min,max) of the maximum serum concentration of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose.
| ug/mL | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|
| Maximum Serum Concentration of Nivolumab as a Single Agent or in Combination With Ipilimumab | 80.9 (56.9 to 119.4) | 72 (39.0 to 93.7) | 68.1 (37.6 to 224.9) | 17.3 (14.4 to 23.1) | 43.3 (35.4 to 48.6) | 41.7 (23.2 to 74.4) | 34.6 (15.9 to 61.7) | 49.1 (10.0 to 62.5) |
Median (min,max) of the minimum serum concentration of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose.
| ug/mL | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|
| Minimum Serum Concentration of Nivolumab as a Single Agent or in Combination With Ipilimumab | 29.6 (13.7 to 60.9) | 30.4 (9.7 to 46.7) | 26.4 (8.9 to 85.3) | 3.8 (2.0 to 5.6) | 10.5 (7.4 to 14.0) | 9.2 (7.9 to 12.9) | 10.8 (2.9 to 30.0) | 8 (7.7 to 12.8) |
Median (min,max) of the clearance of nivolumab as a single agent or in combination with ipilimumab by study part and dose level. Measured during cycle 1 at 0, 24, 72, 192, and 360 hours post-dose.
| mL/hr/kg | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab |
|---|---|---|---|
| Clearance of Nivolumab as a Single Agent or in Combination With Ipilimumab | 0.1 (0.1 to 0.3) | 0.2 (0.1 to 0.3) | 0.1 (0.0 to 0.5) |
Median (min, max) of PD-L1 expression levels by study part, dose level, and disease cohort.
| percent | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B1: 3 mg/kg Nivolumab | Part B2: 3 mg/kg Nivolumab | Part B3: 3 mg/kg Nivolumab | Part B4: 3 mg/kg Nivolumab | Part B5: 3 mg/kg Nivolumab | Part B6: 3 mg/kg Nivolumab | Part B7: 3 mg/kg Nivolumab | Part B8: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D2: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D3: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D4: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E3: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | Part E4: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PD-L1 Expression of Nivolumab as a Single Agent or in Combination With Ipilimumab | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) | 2.5 (0.0 to 70.0) | 0 (0.0 to 1.0) | 0 (0.0 to 3.0) | 0 (0.0 to 1.0) | 100 (30.0 to 100.0) | 7.5 (0.0 to 100.0) | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) | 0 (0.0 to 97.0) | 3 (0.0 to 100.0) | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) | 0 (0.0 to 3.0) | 0 (0.0 to 25.0) | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
Median (min, max) expression levels by biomarker, dose level, study part, and disease cohort.
No measurements were reported for this outcome.
Collected over Up to 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A: 3 mg/kg Nivolumab | 3/7 (42.9%) | 6/7 (85.7%) | 7/7 (100%) |
| Part A PK: 3 mg/kg Nivolumab | 3/6 (50%) | 6/6 (100%) | 6/6 (100%) |
| Part B: 3 mg/kg Nivolumab | 38/72 (52.8%) | 70/72 (97.2%) | 72/72 (100%) |
| Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | 2/6 (33.3%) | 4/6 (66.7%) | 6/6 (100%) |
| Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | 4/6 (66.7%) | 6/6 (100%) | 6/6 (100%) |
| Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | 4/6 (66.7%) | 5/6 (83.3%) | 6/6 (100%) |
| Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | 19/29 (65.5%) | 26/29 (89.7%) | 29/29 (100%) |
| Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | 1/8 (12.5%) | 7/8 (87.5%) | 8/8 (100%) |
| Event | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, PROGRESSIVE DISEASENeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/7 | 2/6 | 30/72 | 2/6 | 3/6 | 4/6 | 9/29 | 0/8 |
| Lymphocyte count decreasedInvestigations | 3/7 | 3/6 | 35/72 | 1/6 | 3/6 | 0/6 | 12/29 | 5/8 |
| Neutrophil count decreasedInvestigations | 3/7 | 1/6 | 26/72 | 0/6 | 1/6 | 1/6 | 2/29 | 2/8 |
| Platelet count decreasedInvestigations | 3/7 | 0/6 | 21/72 | 0/6 | 1/6 | 1/6 | 4/29 | 1/8 |
| AnemiaBlood and lymphatic system disorders | 0/7 | 2/6 | 25/72 | 1/6 | 1/6 | 2/6 | 8/29 | 2/8 |
| Aspartate aminotransferase increasedInvestigations | 0/7 | 0/6 | 4/72 | 0/6 | 2/6 | 0/6 | 3/29 | 1/8 |
| HyponatremiaMetabolism and nutrition disorders | 1/7 | 1/6 | 5/72 | 2/6 | 1/6 | 0/6 | 4/29 | 0/8 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 1/7 | 2/6 | 4/72 | 0/6 | 0/6 | 0/6 | 5/29 | 1/8 |
| White blood cell decreasedInvestigations | 1/7 | 2/6 | 19/72 | 0/6 | 1/6 | 1/6 | 3/29 | 2/8 |
| Alanine aminotransferase increasedInvestigations | 0/7 | 0/6 | 5/72 | 1/6 | 0/6 | 0/6 | 2/29 | 2/8 |
| Event | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab |
|---|---|---|---|---|---|---|---|---|
| AnemiaBlood and lymphatic system disorders | 6/7 | 6/6 | 62/72 | 5/6 | 6/6 | 6/6 | 20/29 | 6/8 |
| ConstipationGastrointestinal disorders | 3/7 | 6/6 | 28/72 | 2/6 | 3/6 | 2/6 | 14/29 | 3/8 |
| FatigueGeneral disorders | 4/7 | 4/6 | 48/72 | 2/6 | 4/6 | 3/6 | 20/29 | 8/8 |
| HyperglycemiaMetabolism and nutrition disorders | 3/7 | 3/6 | 29/72 | 3/6 | 3/6 | 3/6 | 11/29 | 7/8 |
| Lymphocyte count decreasedInvestigations | 5/7 | 3/6 | 37/72 | 3/6 | 2/6 | 2/6 | 17/29 | 7/8 |
| HypoalbuminemiaMetabolism and nutrition disorders | 2/7 | 4/6 | 43/72 | 3/6 | 3/6 | 5/6 | 14/29 | 6/8 |
| ProteinuriaRenal and urinary disorders | 1/7 | 0/6 | 20/72 | 1/6 | 5/6 | 4/6 | 11/29 | 4/8 |
| Abdominal painGastrointestinal disorders | 1/7 | 2/6 | 22/72 | 1/6 | 2/6 | 1/6 | 8/29 | 6/8 |
| Aspartate aminotransferase increasedInvestigations | 5/7 | 3/6 | 36/72 | 3/6 | 3/6 | 4/6 | 10/29 | 6/8 |
| HypocalcemiaMetabolism and nutrition disorders | 4/7 | 3/6 | 36/72 | 3/6 | 3/6 | 2/6 | 9/29 | 6/8 |
| Age, Categorical(Participants) | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| <=18 years | 7 | 6 | 59 | 6 | 6 | 6 | 18 | 4 | 112 |
| Between 18 and 65 years | 0 | 0 | 13 | 0 | 0 | 0 | 11 | 4 | 28 |
| >=65 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| Median | 12 (5 to 13) | 9.5 (7 to 15) | 15 (1 to 27) | 15 (12 to 15) | 14.5 (11 to 17) | 8.5 (4 to 27) | 17 (5 to 27) | 19 (11 to 28) | 15 (1 to 28) |
| Sex: Female, Male(Participants) | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| Female | 5 | 1 | 28 | 1 | 3 | 4 | 8 | 5 | 55 |
| Male | 2 | 5 | 44 | 5 | 3 | 2 | 21 | 3 | 85 |
| Ethnicity (NIH/OMB)(Participants) | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 2 | 1 | 9 | 1 | 1 | 1 | 5 | 1 | 21 |
| Not Hispanic or Latino | 5 | 5 | 62 | 5 | 5 | 5 | 23 | 7 | 117 |
| Unknown or Not Reported | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 |
| Race (NIH/OMB)(Participants) | Part A: 3 mg/kg Nivolumab | Part A PK: 3 mg/kg Nivolumab | Part B: 3 mg/kg Nivolumab | Part C: 1mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part C PK: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part D: 3mg/kg Nivolumab and 1mg/kg Ipilimumab | Part E: 1mg/kg Nivolumab and 3mg/kg Ipilimumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Asian | 0 | 0 | 5 | 1 | 1 | 0 | 0 | 0 | 7 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 8 | 1 | 1 | 0 | 2 | 0 | 12 |
| White | 7 | 6 | 51 | 3 | 4 | 4 | 23 | 8 | 106 |
| More than one race | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 2 |
| Unknown or Not Reported | 0 | 0 | 6 | 1 | 0 | 1 | 4 | 0 | 12 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Mar 2015 to primary completion in Sep 2021, 78 months.
Results were first posted in Jan 2023, 1 year 3 months after primary completion.
Of 85 non-industry phase 1/2 interventional studies under Melanoma, half reached primary completion within 59 months of starting (the median), counting those still running; a quarter within 47 and three quarters within 98. This study's 78 months is above that.
Counting every sponsor, half of 220 studies reached it within 61 months; a quarter within 42 and three quarters within 85.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Ipilimumab · Nivolumab
National Cancer Institute (NCI) →