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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Biological: Nivolumab; Biological: Daratumumab

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Local Institution
• Canada
  • Edmonton, Canada, T6G 1Z2
    • Local Institution
• France
  • Lyon Cedex 08, France, 69373
    • Local Institution
  • Marseille Cedex 9, France, 13273
    • Local Institution
  • Strasbourg Cedex, France, 67085
    • Centre Paul Strauss
• Germany
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus
  • Freiburg, Germany, 79106
    • Medizinische Universitaetsklinik Freiburg
  • Heidelberg, Germany, 69120
    • Universitaetsklinik Heidelberg
• Italy
  • Milano, Italy, 20132
    • Local Institution
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Pascale
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigacion
• Spain
  • Madrid, Spain, 28007
    • Hospital Gral. Univ. Gregorio Maranon
  • Majadahonda - Madrid, Spain, 28222
    • Local Institution
• Switzerland
  • Basel, Switzerland, 4031
    • Klinik Fur Onkologie
  • Lausanne, Switzerland, 1011
    • University Hospital of Lausanne
• United States
  • California
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Janssen Biotech, Inc.

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2017
• Primary Completion (Actual): July 6, 2020
• Study Completion (Actual): July 6, 2020

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: March 28, 2017
• First Posted (Actual): March 31, 2017

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 2, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer (NSCLC); Triple Negative Breast Cancer (TNBC); Pancreatic Cancer (PAC)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Daratumumab
• Other Study ID Numbers: CA209-9GW; 2017-000367-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No