Skip to main content
OpenTrials
Completed

NCT Number: NCT03668119

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)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Pan Tumor

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Local Institution - 0016, Ciudad Autonoma Beunos Aires, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Nivolumab

Biological

Specified dose on specified days

Other names: Opdivo, BMS-936558

Ipilimumab

Biological

Specified dose on specified days

Other names: Yervoy, BMS-734016

Primary outcomes

  1. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A

    Time frame: From date of randomization up to 42 months

    ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on Blinded Independent Central Review (BICR) assessment.

    RECIST Criteria:

    CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.

    PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    RANO Criteria:

    CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

Secondary outcomes

  1. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm B

    Time frame: From date of randomization up to 57 months

    ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on Blinded Independent Central Review (BICR) assessment.

    RECIST Criteria:

    CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.

    PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    RANO Criteria:

    CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

  2. Objective Response Rate (ORR) Per Investigator

    Time frame: From date of randomization up to 57 months

    ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on investigator assessment. Calculated using Clopper-Pearson method.

    RECIST Criteria:

    CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.

    PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    RANO Criteria:

    CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

  3. Duration of Response (DoR) Per Investigator

    Time frame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)

    DoR was defined as the time from first confirmed complete or partial response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Calculated using KM method.

    RECIST Criteria:

    CR= Disappearance of all target lesions. PR= ≥ 30% decrease in the sum of diameters of target lesions. PD= ≥ 20% increase in the sum of diameters of target lesions.

    RANO Criteria:

    CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable/improved T2/FLAIR; off corticosteroids; stable/improved clinically PR= ≥ 50% decrease in the sum of diameters of all measurable enhancing lesions; no progression of nonmeasurable disease; no new lesions; stable/improved T2/FLAIR; stable/improved clinically.

    PD= ≥ 25% increase in sum of diameters of enhancing lesions, on stable/increasing doses of corticosteroids; significant increase in T2/FLAIR; any new lesion; clear clinical deterioration or clear progression of nonmeasurable disease.

  4. Duration of Response (DoR) Per Blinded Independent Central Review (BICR)

    Time frame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)

    DoR was defined as the time from first confirmed complete or partial response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Calculated using KM method.

    RECIST Criteria:

    CR= Disappearance of all target lesions. PR= ≥ 30% decrease in the sum of diameters of target lesions. PD= ≥ 20% increase in the sum of diameters of target lesions.

    RANO Criteria:

    CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable/improved T2/FLAIR; off corticosteroids; stable/improved clinically PR= ≥ 50% decrease in the sum of diameters of all measurable enhancing lesions; no progression of nonmeasurable disease; no new lesions; stable/improved T2/FLAIR; stable/improved clinically.

    PD= ≥ 25% increase in sum of diameters of enhancing lesions, on stable/increasing doses of corticosteroids; significant increase in T2/FLAIR; any new lesion; clear clinical deterioration or clear progression of nonmeasurable disease.

  5. Time to Objective Response (TTR) Per Investigator

    Time frame: From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months)

    TTR is defined as the time from randomization date to the date of the first confirmed response (complete response (CR) or partial response (PR)), based on investigator assessment.

    RECIST Criteria:

    CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.

    PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    RANO Criteria:

    CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

  6. Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)

    Time frame: From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months)

    TTR is defined as the time from randomization date to the date of the first confirmed response (complete response (CR) or partial response (PR)), based on Blinded Independent Central Review (BICR) assessment.

    RECIST Criteria:

    CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.

    PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    RANO Criteria:

    CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

  7. Clinical Benefit Rate (CBR) Per Investigator

    Time frame: From date of randomization up to 57 months

    CBR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD) based on investigator assessment.

    RECIST Criteria:

    CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm PR= ≥ 30% decrease in the sum of diameters of target lesions SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

    RANO Criteria:

    CR= Disappearance of all enhancing disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions; stable or improved clinically SD= does not qualify for CR, PR, or progression; stable nonenhancing T2/FLAIR lesions

  8. Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)

    Time frame: From date of randomization up to 57 months

    CBR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD) per Blinded Independent Central Review (BICR) assessment.

    RECIST Criteria:

    CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm PR= ≥ 30% decrease in the sum of diameters of target lesions SD= does not qualify for PR or progressive disease

    RANO Criteria:

    CR= Disappearance of all enhancing disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions; stable or improved clinically SD= does not qualify for CR, PR, or progression; stable nonenhancing T2/FLAIR lesions

  9. Progression Free Survival (PFS) Per Investigator

    Time frame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)

    PFS is defined as the time from randomization date to the date of the first documented tumor progression, determined by investigator assessment, or death due to any cause, whichever occurs first. Calculated using KM method.

    RECIST Criteria:

    Progressive Disease (PD)= ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm.

    RANO Criteria:

    PD= ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids; significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy; any new lesion; clear clinical deterioration or clear progression of nonmeasurable disease.

  10. Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)

    Time frame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)

    PFS is defined as the time from randomization date to the date of the first documented tumor progression, determined by Blinded Independent Central Review (BICR) assessment, or death due to any cause, whichever occurs first. Calculated using KM method.

    RECIST Criteria:

    Progressive Disease (PD)= ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm.

    RANO Criteria:

    PD= ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids; significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy; any new lesion; clear clinical deterioration or clear progression of nonmeasurable disease.

  11. Overall Survival (OS)

    Time frame: From date of randomization to date of death (Up to 57 months)

    OS is defined as the time between the date of randomization and the date of death due to any cause. Participants who did not have a date of death were censored on the last date for which a participant was known to be alive. Calculated using KM method.

  12. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: From first dose to 30 days post last dose (Up to 25 months)

    Number of participants with any grade adverse events (AEs), serious adverse events (SAEs), drug-related AEs, and drug-related SAEs by Tumor Mutational Burden- High (TMB-H) status using worst grade per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5 criteria. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

    TMB-H = ≥ 10 mutations per megabase bTMB-H and tTMB-H are not mutually exclusive

  13. Number of Participants With On-Treatment Laboratory Parameters

    Time frame: From first dose to 30 days post last dose (Up to 25 months)

    Number of participants with grade 3-4 on-treatment laboratory parameters. Parameters include hematology, chemistry, liver function, and renal function using worst grade per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5 criteria.

    Grade 3=Severe event Grade 4=Life threatening event TMB-H = ≥ 10 mutations per megabase bTMB-H and tTMB-H are not mutually exclusive

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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)

Acronym: CheckMate 848

Important dates

Study start
2018
Primary completion
2022
Study completion
2023
First posted
Sep 12, 2018
Registry last updated
Aug 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.