A Study to Test the Safety and Effectiveness of Nivolumab Combined With Daratumumab in Patients With Pancreatic, Non-Small Cell Lung or Triple Negative Breast Cancers, That Have Advanced or Have Spread

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether a combination of Nivolumab and Daratumumab is safe and effective when treating Pancreatic, Non-Small Cell Lung or Triple Negative Breast Cancers, that have advanced or have spread.

Official Title
-----------------
Phase 1/2 Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab Combined With Daratumumab in Participants With Advanced or Metastatic Solid Tumors

Conditions
-----------------
Advanced Cancer

Intervention / Treatment
-----------------
* Biological: Nivolumab
* Biological: Daratumumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Patients with metastatic or advanced solid tumors Women with histologically or cytologically confirmed triple negative breast carcinoma Participants with histologically or cytologically confirmed pancreatic adenocarcinoma Participants with histologically or cytologically confirmed Non Small Cell Lung Cancer (NSCLC) Exclusion Criteria: Active brain metastases or leptomeningeal metastases. Any serious or uncontrolled medical disorder Prior malignancy active within the previous 3 years Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunotherapy Combination<br>TNBC and PAC participants who are deriving clinical benefit will continue to be treated with the nivolumab plus daratumumab combination therapy | Biological: Nivolumab<br>* Specified dose on specified days<br>Biological: Daratumumab<br>* Specified dose on specified days<br>|
| Experimental: Nivolumab Monotherapy<br>NSCLC patients who are deriving clinical benefit will be treated with nivolumab monotherapy | Biological: Nivolumab<br>* Specified dose on specified days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | Number of participants with any grade of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Daratumumab | From first dose to 30 days post last dose (up to 34 months) | 
| Number of Participants With Serious Adverse Events (SAEs) | Number of participants with any grade of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Daratumumab | From first dose to 30 days post last dose (up to 34 months) | 
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Number of participants with laboratory abnormalities in specific liver tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN Total bilirubin > 2 x ULN ALP > 1.5 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN | From first dose to 30 days post last dose (up to 34 months) | 
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of subjects with the following laboratory abnormalities from on-treatment evaluations will be summarized: TSH value > ULN and with baseline TSH value <= ULN with at least one FT3/FT4 test value < LLN within 2-week window after the abnormal TSH test with all FT3/FT4 test values >= LLN within 2-week window after the abnormal TSH test with FT3/FT4 missing within 2-week window after the abnormal TSH test. TSH < LLN and with baseline TSH value >= LLN with at least one FT3/FT4 test value > ULN within 2-week window after the abnormal TSH test with all FT3/FT4 test values <= ULN within 2-week window after the abnormal TSH test with FT3/FT4 missing within 2-week window after the abnormal TSH test | From first dose to 30 days post last dose (up to 34 months) | 
| Number of Participants With Laboratory Results of Worst CTC Grade | Number of participants with laboratory test results of worst (CTC v4.0) grades 0-4 to determine the safety and tolerability of Nivolumab and Daratumumab | From first dose to 30 days post last dose (up to 34 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate (ORR) is defined as the percentage of treated participants who achieve a best response of complete response (CR) or partial response (PR) based on investigator assessments (using RECIST v1.1 criteria) | Up to 36 months | 
| Duration of Response (DOR) | Duration of response (DOR) is defined as the time between the date of first documented response (Complete response or partial response) to the date of the first documented tumor progression as determined by Investigator (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first | Up to 36 months | 
| Best Overall Response (BOR) | Best overall response (BOR) is defined as the best response, as determined by Investigator, recorded between the date of first dose and the date of objectively documented progression per RECIST v1.1 criteria or the date of subsequent therapy, whichever occurs first. | Up to 36 months | 
| Progression Free Survival (PFS) | Progression Free Survival (PFS) is defined as the time between the date of treatment start day and the date of first documented tumor progression, based on Investigator assessments (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. | Up to 36 months | 
| Nivolumab Serum Concentrations | Pharmacokinetics (PK) assessed using serum concentration data for Nivolumab | From day 1 to follow-up 2 (up to 36 months) | 
| Daratumumab Serum Concentrations | Pharmacokinetics (PK) assessed using serum concentration data for Daratumumab | From day 1 to follow-up 2 (up to 36 months) | 
| Percentage of Participants Anti Drug Antibody (ADA) by Positivity | Percentage of participants Anti Drug Antibody (ADA) to assess immunogenicity by ADA positive status and ADA negative status, relative to baseline. ADA positive is a participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment. ADA Negative is a participant with no ADA-positive sample after initiation of treatment | Up to 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-small cell lung cancer (NSCLC), Triple Negative Breast Cancer (TNBC), Pancreatic Cancer (PAC)