An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers

Study Overview
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Brief Summary
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A study to evaluate the safety of Nivolumab given in combination with Ipilimumab in patients with advanced cancers. The initial group will enroll patients with newly diagnosed Stage 4 or non-small cell lung cancer that has come back.

Official Title
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A Phase 3b/4 Safety Trial of Flat Dose Nivolumab In Combination With Ipilimumab in Participants With Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Nivolumab in combination with Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Stage 4 or recurrent non-small cell lung cancer Eastern Cooperative Oncology Group (ECOG) score 0-1 (Physically able to carry out light housework or office work through to being fully active as you were before cancer) No prior systemic anticancer therapy (including EGFR and ALK inhibitors) Tissue or Programmed death-ligand 1 (PD-L1) results available Cohort 1A Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) score 2 or Eastern Cooperative Oncology Group (ECOG) score 0-1 and one disease specific criteria as listed in the protocol Cohort C Inclusion Criteria: High Tumor Mutation Burden Exclusion Criteria: Untreated brain metastases An active malignancy that requires concurrent intervention Active, known or suspected autoimmune disease Carcinomatous meningitis, which means there is inflammation of the covering of the brain, caused by cancer Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab in combination with Ipilimumab<br>Specified dose on specified days | Drug: Nivolumab in combination with Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy (Ipilimumab);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Drug related AEs are those events with relationship to study drug. If the relationship to study drug is missing, the AE will be considered as drug-related. The select AEs of interest are the following: Pulmonary, Renal, Gastrointestinal, Hepatic, Skin, Endocrine, and hypersensitivity/infusion reaction events. AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death | From first dose to 30 days post last dose (Up to approximately 27 months) | 
| Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | imAEs are specific events that include pneumonitis, diarrhea/colitis, hepatitis, nephritis/renal dysfunction, rash, and endocrine (adrenal insufficiency, hypothyroidism/thyroiditis, hyperthyroidism, diabetes mellitus, and hypophysitis). AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death | From first dose to 100 days post last dose (Up to approximately 29 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression. | From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months) | 
| Overall Survival (OS) | OS is defined as the time from first dosing date to the date of death. A participant who has not died will be censored at last known date alive. | From first dosing date to the date of death (Up to approximately 67 months) | 
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR). CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) 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. | From first dosing date up to approximately 67 months | 
| Duration of Response (DoR) | DoR is defined as the time between the date of first confirmed complete response (CR) or partial response (PR) to the date of the first documented tumor progression per RECIST 1.1, or death due to any cause, whichever occurs first. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) 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. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression. | From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months) | 
| Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | FACT-L is a quality-of-life questionnaire which includes Lung Cancer Subscale (LCS) that assesses the treatment impact on lung cancer related symptoms in 5 domains: Physical, social/family, emotional, and functional well-being using a 5-point scale (0=not at all; 1=a little bit, 2=somewhat; 3=quite a bit; 4=very much) added to obtain total score. The ranges of possible total scores are 0-136 for the FACT-L with a higher score representing better quality of life, improved symptomatology and enhanced physical/functional outcomes. According to Functional Assessment of Chronic Illness Therapy scoring guidelines, in the event of missing responses for some of the questions, scores will be prorated using the average of the other answers in that scale. Baseline is defined as events that occur before the date/time of first dose. Post treatment visits include follow-up (FU) visit 1, FU visit 2, and subsequent survival FU visits to occur every 3 months up until survival FU visit 18. | From baseline and up to subsequent survival follow-up visit 18 (Up to approximately 67 months) |