An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread (CheckMate142)

• ClinicalTrials.gov Identifier: NCT02060188
• Recruitment Status: Active, not recruiting
• First Posted: February 11, 2014
• Last Update Posted: November 6, 2019
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

Brief Summary:

The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination with other anti-cancer drugs, will result in meaningful tumor size reduction, in patients with colon cancer that has come back or has spread, and who have a specific biomarker in their tumors.

Condition or disease	Intervention/treatment	Phase
Microsatellite Unstable Colorectal Cancer; Microsatellite Stable Colorectal Cancer; Mismatch Repair Proficient Colorectal Cancer; Mismatch Repair Deficient Colorectal Cancer	Drug: Ipilimumab; Drug: Nivolumab; Drug: Cobimetinib; Drug: Daratumumab; Drug: anti-LAG-3 antibody	Phase 2

Detailed Description:

Allocation: The Microsatellite Instability High (MSI-High) and C4 and C6 Cohort Parts of the trial are Non-randomized, The Non-MSI high Dose Escalation Phase part of the trial contained a randomized portion

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 340 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Clinical Trial of Nivolumab, or Nivolumab Combinations in Recurrent and Metastatic Microsatellite High (MSI-H) and Non-MSI-H Colon Cancer
• Actual Study Start Date: March 7, 2014
• Estimated Primary Completion Date: July 6, 2022
• Estimated Study Completion Date: July 6, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nivolumab Monotherapy; Nivolumab administered as IV infusion at a dose of 3mg/kg every 2 weeks until disease progression	Drug: Nivolumab; Other Names: BMS-936558; Opdivo
Experimental: Nivolumab (Nivo) + Ipilimumab (Ipi); Nivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3 week (wk) for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression; Dose Escalation Phase: (Complete); Dose Level (DL) 1: Nivo 0.3mg/Kg with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression; DL 1: Nivo 1mg/Kg IV with Ipi 1 mg/Kg IV every 3 wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression; DL 2a: Nivo 1mg/Kg IV with Ipi 3 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression; DL 2b: Nivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression	Drug: Ipilimumab; Other Name: Yervoy; Drug: Nivolumab; Other Names: BMS-936558; Opdivo
Experimental: Nivolumab (Nivo) + Ipilimumab (Ipi) Cohort C3; Nivo IV dosed every 2wk with Ipi IV dosed every 6wk.	Drug: Ipilimumab; Other Name: Yervoy; Drug: Nivolumab; Other Names: BMS-936558; Opdivo
Experimental: Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib Cohort C4; Nivo IV dosed every 2wk, with Ipi IV dosed every 6wk, combined with Cobimetinib dosed orally once daily 21 days on/7 days off.	Drug: Ipilimumab; Other Name: Yervoy; Drug: Nivolumab; Other Names: BMS-936558; Opdivo; Drug: Cobimetinib; Other Name: Cotellic
Experimental: Nivolumab (Nivo) + BMS-986016 Cohort C5; Nivo IV dosed every 2wk with BMS-986016 dosed every 2 wk	Drug: Nivolumab; Other Names: BMS-936558; Opdivo; Drug: anti-LAG-3 antibody; Other Name: BMS-986016
Experimental: Nivolumab (Nivo) + Daratumumab Cohort C6; Daratumumab IV dosed weekly for week 1-8; then every 2 wks from Week 9-24; then every 4 wks on week 25; with Nivo dosed every 2 wks starting at week 3 and every 4 wks starting at week 25	Drug: Nivolumab; Other Names: BMS-936558; Opdivo; Drug: Daratumumab; Other Name: Darzalex

Outcome Measures

Primary Outcome Measures :

1. Objective response rate (ORR) in all MSI-High and non-MSI-High subjects as determined by Investigators [ Time Frame: The final analysis of the primary endpoint will occur at least 6 months after the last enrolled subject's first dose of study therapy (Approximately up to 34 months) ]
   (Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later)) (Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later))

Secondary Outcome Measures :

1. ORR in all MSI-H and non-MSI-H subjects based on IRRC determination [ Time Frame: The final analysis of the secondary endpoint will occur the time of the primary endpoint analysis (Approximately up to 34 months) ]
   Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/- wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued(whichever occurs later)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Men and women ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Histologically confirmed recurrent or metastatic colorectal cancer
• Measurable disease by CT or MRI

• Testing for MSI Status (by an accredited lab)

  1. Subjects with microsatellite instability high (MSI-H) tumors will enroll in the MSI-H Cohort (mStage and cStage groups), the C3 Cohort, and the C5 Cohort.
  2. Subjects with phenotypes that are non-microsatellite instability high (non-MSI-H) will enroll in the non- MSI-H Safety Cohort and the C6, C4 Cohorts.
• Adequate organ function as defined by study-specific laboratory tests
• Must use acceptable form of birth control throughout the study. After the final dose of study drug, an acceptable form of birth control must be used for 23 weeks for women of childbearing potential (WOCBP) and 31 weeks for men who are sexually active with WOCBP
• Signed informed consent
• Willing and able to comply with study procedures
• Subjects enrolled into the C3 Cohort must have not had treatment for their metastatic disease

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases are not allowed.
• Prior treatment with an anti-Programmed Death Receptor (PD)-1, anti-PD-L1, anti-PD-L2, anti-Cytotoxic T-Cell Lymphoma-4 Antigen (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Prior malignancy active within the previous 3 years except for locally curable cancers
• Subjects with active, known or suspected autoimmune disease
• Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Locations

United States, Arizona

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

United States, California

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

Pacific Hematology Oncology Associates

San Francisco, California, United States, 94115

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Dana Farber Cancer Institute.

Boston, Massachusetts, United States, 02114

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Minnesota

Allina Health System

Minneapolis, Minnesota, United States, 55407

United States, North Carolina

Duke University Office of Research Administration

Durham, North Carolina, United States, 27710

Novant Health Oncology Specialists

Winston-Salem, North Carolina, United States, 27103

United States, Oregon

Providence Cancer Center Oncology and Hematology Care- Eastside

Portland, Oregon, United States, 97213

United States, Pennsylvania

Lehigh Valley Hospital

Allentown, Pennsylvania, United States, 18103

University Of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States, 15232

United States, Tennessee

Vanderbilt University Med Ctr

Nashville, Tennessee, United States, 37232-0021

United States, Texas

Md Anderson Can Cnt

Houston, Texas, United States, 77030-4009

Australia, New South Wales

Westmead Hospital

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Tasman Oncology Research Pty Ltd

Southport, Queensland, Australia, 4215

Australia, Victoria

Royal Melbourne Hospital

Parkville, Victoria, Australia, 3050

Belgium

Local Institution

Brussels, Belgium, 1000

Local Institution

Brussels, Belgium, 1090

Local Institution

Leuven, Belgium, 3000

Canada, Alberta

Local Institution

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

Local Institution

Toronto, Ontario, Canada, M5G 1X5

France

Local Institution

Paris, France, 75012

Ireland

Local Institution

Dublin 4, Ireland

Local Institution

Dublin 9, Ireland

Local Institution

Galway, Ireland

Italy

Local Institution

Candiolo, TO, Italy, 10060

Local Institution

Modena, Italy, 41124

Local Institution

Padova, Italy, Padova

Spain

Local Institution

Madrid, Spain, 28009

Local Institution

Madrid, Spain, 28050

Local Institution

Sevilla, Spain, 41013

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information  BMS Clinical Trial Patient Recruiting  Investigator Inquiry Form  FDA Safety Alerts and Recalls 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. doi: 10.1200/JCO.2017.76.9901. Epub 2018 Jan 20.

Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. doi: 10.1016/S1470-2045(17)30422-9. Epub 2017 Jul 19. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02060188
• Other Study ID Numbers: CA209-142; 2013-003939-30 ( EudraCT Number )
• First Posted: February 11, 2014
• Last Update Posted: November 6, 2019
• Last Verified: November 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Nivolumab; Ipilimumab; Daratumumab; Antibodies; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological; Antineoplastic Agents