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) (CheckMate 848)

• ClinicalTrials.gov Identifier: NCT03668119
• Recruitment Status: Active, not recruiting
• First Posted: September 12, 2018
• Last Update Posted: March 16, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: September 11, 2018
• First Posted Date: September 12, 2018
• Last Update Posted Date: March 16, 2023
• Actual Study Start Date: October 31, 2018
• Actual Primary Completion Date: May 3, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 28, 2022): Blinded independent central review (BICR)-assessed Objective Response Rate (ORR) in participants treated with nivolumab combined with ipilimumab [ Time Frame: Approximately 3 years ]

Original Primary Outcome Measures (submitted: September 11, 2018)

Objective Response Rate (ORR) [ Time Frame: Approximately 3 years ]

Assessed by blinded independent central review (BICR)

Current Secondary Outcome Measures (submitted: February 28, 2022)

• BICR-assessed ORR in participants treated with nivolumab monotherapy [ Time Frame: Approximately 3 years ]
• Investigator-assessed ORR in participants treated with nivolumab combined with ipilimumab and nivolumab monotherapy [ Time Frame: Approximately 3 years ]
• Duration of response (DOR) [ Time Frame: Approximately 3 years ]
• Time To Response (TTR) [ Time Frame: Approximately 3 years ]
• Clinical benefit rate (CBR) [ Time Frame: Approximately 3 years ]
• BICR assessed Progression Free Survival (PFS) [ Time Frame: Approximately 3 years ]
• Investigator assessed PFS [ Time Frame: Approximately 3 years ]
• Overall survival (OS) [ Time Frame: Approximately 3 years ]
• Number of participants with Adverse Events (AEs) [ Time Frame: Approximately 3 years ]
• Number of participants with clinical laboratory abnormalities [ Time Frame: Approximately 3 years ]

Original Secondary Outcome Measures (submitted: September 11, 2018)

• Duration of response (DOR) [ Time Frame: Approximately 3 years ]
  Assessed by BICR and investigator
• ORR [ Time Frame: Approximately 3 years ]
  Assessed by investigator
• TTR [ Time Frame: Approximately 3 years ]
  Assessed by BICR and investigator
• Clinical benefit rate (CBR) [ Time Frame: Approximately 3 years ]
  Assessed by BICR and investigator
• Overall survival (OS) [ Time Frame: Approximately 3 years ]
• PFS [ Time Frame: Approximately 3 years ]
  Assessed by BICR and investigator
• Incidence of Adverse Events (AEs) [ Time Frame: Approximately 3 years ]
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Approximately 3 years ]
• Incidence of laboratory abnormalities [ Time Frame: Approximately 3 years ]
• Incidence of anti-drug antibody (ADA) [ Time Frame: Approximately 3 years ]
  Measured by immunoassay

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pan Tumor

Intervention

• Biological: Nivolumab
  Specified dose on specified days
  Other Names:

  • Opdivo
  • BMS-936558
• Biological: Ipilimumab
  Specified dose on specified days
  Other Names:

  • Yervoy
  • BMS-734016

Study Arms

• Experimental: Nivolumab + Ipilimumab Combination
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Experimental: Nivolumab Monotherapy
  Intervention: Biological: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 13, 2021): 212
• Original Estimated Enrollment (submitted: September 11, 2018): 159
• Estimated Study Completion Date: October 31, 2023
• Actual Primary Completion Date: May 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants with a refractory, metastatic, or unresectable histologically or cytologically confirmed solid malignant tumor with high tumor mutational burden (TMB-H) who are refractory to standard local therapies, or for which no standard treatment is available.
• Must be able to provide tissue and blood TMB-H testing results
• Must have measurable disease for response assessment

Exclusion Criteria:

• Participants with melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or hematological malignancy as primary site of disease
• Participants who received prior treatment with an anti-programmed death-1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), anti-programmed death ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment

Other protocol defined inclusion/exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Canada, Chile, Denmark, France, Germany, Italy, Netherlands, Poland, Puerto Rico, Romania, Singapore, Spain, United Kingdom, United States
• Removed Location Countries: Brazil, Peru

Administrative Information

• NCT Number: NCT03668119
• Other Study ID Numbers: CA209-848; 2016-002898-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: March 2023