Working… Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03668119
Recruitment Status : Recruiting
First Posted : September 12, 2018
Last Update Posted : November 17, 2020
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of this study is to determine whether nivolumab plus ipilimumab or nivolumab alone is effective and safe in the treatment of solid tumors with High Tumor Mutational Burden (TMB-H)

Condition or disease Intervention/treatment Phase
Pan Tumor Biological: Nivolumab Biological: Ipilimumab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 183 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 29, 2018
Estimated Primary Completion Date : June 15, 2021
Estimated Study Completion Date : October 31, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Nivolumab + Ipilimumab Combination Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
  • BMS-936558

Biological: Ipilimumab
Specified dose on specified days
Other Names:
  • Yervoy
  • BMS-734016

Experimental: Nivolumab Monotherapy Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
  • BMS-936558

Primary Outcome Measures :
  1. Objective Response Rate (ORR) in the Tissue Tumor Mutational Burden (tTMB-H) Population [ Time Frame: Approximately 3 years ]
  2. Objective Response Rate (ORR) in the Blood Tumor Mutational Burden (bTMB-H) Population [ Time Frame: Approximately 3 years ]

Secondary Outcome Measures :
  1. Duration of response (DOR) [ Time Frame: Approximately 3 years ]
  2. Objective Response Rate (ORR) [ Time Frame: Approximately 3 years ]
  3. Time To Response (TTR) [ Time Frame: Approximately 3 years ]
  4. Clinical benefit rate (CBR) [ Time Frame: Approximately 3 years ]
  5. Overall survival (OS) [ Time Frame: Approximately 3 years ]
  6. Progression Free Survival (PFS) [ Time Frame: Approximately 3 years ]
  7. Incidence of Adverse Events (AEs) [ Time Frame: Approximately 3 years ]
  8. Incidence of Serious Adverse Events (SAEs) [ Time Frame: Approximately 3 years ]
  9. Incidence of AEs leading to discontinuation [ Time Frame: Approximately 3 Years ]
  10. Incidence of Deaths [ Time Frame: Approximately 3 Years ]
  11. Incidence of laboratory abnormalities [ Time Frame: Approximately 3 years ]
  12. Incidence of anti-drug antibody (ADA) [ Time Frame: Approximately 3 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit

Inclusion Criteria:

  • Participants with a refractory, metastatic, or unresectable histologically or cytologically confirmed solid malignant tumor with TMB-H who are refractory to standard local therapies, or for which no standard treatment is available.
  • Available tumor tissue and blood for TMB testing
  • Participants must have measurable disease for response assessment

Exclusion Criteria:

  • Women with positive pregnancy test at enrollment or prior administration of study medication
  • 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-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or 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 could apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03668119

Layout table for location contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email:
Contact: First line of the email MUST contain NCT # and Site #.

Show Show 96 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Layout table for investigator information
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Additional Information:
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb Identifier: NCT03668119    
Other Study ID Numbers: CA209-848
2016-002898-35 ( EudraCT Number )
First Posted: September 12, 2018    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bristol-Myers Squibb:
Additional relevant MeSH terms:
Layout table for MeSH terms
Antineoplastic Agents, Immunological
Antineoplastic Agents