Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Bristol-Myers Squibb

The purpose of this study is to demonstrate the clinical activity of nivolumab in combination with ipilimumab in multiple types of tumors based on their Tumor Mutational Burden status.

A Study of Nivolumab Combined With Ipilimumab and Nivolumab Alone in Patients With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)

A Randomized, Open-Label, Phase 2 Study of Nivolumab in Combination With Ipilimumab or Nivolumab Monotherapy in Participants With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)

ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on Blinded Independent Central Review (BICR) assessment.

RECIST Criteria:

CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.

PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

RANO Criteria:

CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on investigator assessment.

RECIST Criteria:

CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.

PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

RANO Criteria:

CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

DoR was defined as the time from first confirmed complete or partial response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.

RECIST Criteria:

CR= Disappearance of all target lesions. PR= ≥ 30% decrease in the sum of diameters of target lesions. PD= ≥ 20% increase in the sum of diameters of target lesions.

RANO Criteria:

CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable/improved T2/FLAIR; off corticosteroids; stable/improved clinically PR= ≥ 50% decrease in the sum of diameters of all measurable enhancing lesions; no progression of nonmeasurable disease; no new lesions; stable/improved T2/FLAIR; stable/improved clinically.

PD= ≥ 25% increase in sum of diameters of enhancing lesions, on stable/increasing doses of corticosteroids; significant increase in T2/FLAIR; any new lesion; clear clinical deterioration or clear progression of nonmeasurable disease.

TTR is defined as the time from randomization date to the date of the first confirmed response (complete response (CR) or partial response (PR)), based on investigator assessment.

RECIST Criteria:

CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.

PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

RANO Criteria:

CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

TTR is defined as the time from randomization date to the date of the first confirmed response (complete response (CR) or partial response (PR)), based on Blinded Independent Central Review (BICR) assessment.

RECIST Criteria:

CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.

PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

RANO Criteria:

CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

CBR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD) based on investigator assessment.

RECIST Criteria:

CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm PR= ≥ 30% decrease in the sum of diameters of target lesions SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

RANO Criteria:

CR= Disappearance of all enhancing disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions; stable or improved clinically SD= does not qualify for CR, PR, or progression; stable nonenhancing T2/FLAIR lesions

CBR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD) per Blinded Independent Central Review (BICR) assessment.

RECIST Criteria:

CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm PR= ≥ 30% decrease in the sum of diameters of target lesions SD= does not qualify for PR or progressive disease

RANO Criteria:

CR= Disappearance of all enhancing disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions; stable or improved clinically SD= does not qualify for CR, PR, or progression; stable nonenhancing T2/FLAIR lesions

PFS is defined as the time from randomization date to the date of the first documented tumor progression, determined by investigator assessment, or death due to any cause, whichever occurs first.

RECIST Criteria:

Progressive Disease (PD)= ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm.

RANO Criteria:

PD= ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids; significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy; any new lesion; clear clinical deterioration or clear progression of nonmeasurable disease.

PFS is defined as the time from randomization date to the date of the first documented tumor progression, determined by Blinded Independent Central Review (BICR) assessment, or death due to any cause, whichever occurs first.

RECIST Criteria:

Progressive Disease (PD)= ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm.

RANO Criteria:

PD= ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids; significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy; any new lesion; clear clinical deterioration or clear progression of nonmeasurable disease.

OS is defined as the time between the date of randomization and the date of death due to any cause. Participants who do not have a date of death will be censored on the last date for which a participant was known to be alive.

Number of participants with any grade adverse events (AEs), serious adverse events (SAEs), drug-related AEs, and drug-related SAEs by Tumor Mutational Burden- High (TMB-H) status using worst grade per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5 criteria. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

TMB-H = ≥ 10 mutations per megabase bTMB-H and tTMB-H are not mutually exclusive

Number of participants with grade 3-4 on-treatment laboratory parameters. Parameters include hematology, chemistry, liver function, and renal function using worst grade per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5 criteria.

Grade 3=Severe event Grade 4=Life threatening event TMB-H = ≥ 10 mutations per megabase bTMB-H and tTMB-H are not mutually exclusive

The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.

Nivolumab 240 mg Q2W + Ipilimumab 1 mg/kg Q6W

Arm A: Nivolumab+Ipilimumab

Arm B: Nivolumab

Arm B: Nivolumab 240 mg Q2W + Ipilimumab 1 mg/kg Q6W

Arm B: Nivolumab+Ipilimumab (Rollover)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

Blood TMB-H (bTMB-H)

Tissue TMB-H (tTMB-H)

All participants randomized in a salvage setting to arm A by TMB-High status

Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A

All participants randomized in a salvage setting to arm B by TMB-High status

Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm B

All participants randomized in a salvage setting by TMB-High status

Objective Response Rate (ORR) Per Investigator

All responders (CR or PR) randomized in a salvage setting by TMB-High status

Duration of Response (DoR) Per Investigator

Duration of Response (DoR) Per Blinded Independent Central Review (BICR)

Time to Objective Response (TTR) Per Investigator

Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)

Clinical Benefit Rate (CBR) Per Investigator

Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)

Progression Free Survival (PFS) Per Investigator

Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)

Overall Survival (OS)

Blood TMB-H (bTMB-H) AEs

Tissue TMB-H (tTMB-H) AEs

bTMB-H SAEs

tTMB-H SAEs

bTMB-H drug-related AEs

tTMB-H drug-related AEs

bTMB-H drug-related SAEs

tTMB-H drug-related SAEs

All treated participants by TMB-High status

Spots Global Cancer Trial Database for pan tumor

Every month we try and update this database with for pan tumor cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pan tumor

Every month we try and update this database with for pan tumor cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pan tumor cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.