A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer (CHECKMATE 920)
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| ClinicalTrials.gov Identifier: NCT02982954 |
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Recruitment Status :
Completed
First Posted : December 6, 2016
Results First Posted : October 14, 2021
Last Update Posted : November 1, 2022
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Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
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Brief Summary:
To investigate the safety of Nivolumab in combination with Ipilimumab in subjects with previously untreated advanced or metastatic Renal Cell Cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Renal Cell Carcinoma | Drug: Nivolumab Drug: Ipilimumab | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 211 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 3b/4 Safety Trial of Nivolumab Combined With Ipilimumab in Subjects With Previously Untreated, Advanced or Metastatic RCC (CheckMate 920: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 920) |
| Actual Study Start Date : | January 16, 2017 |
| Actual Primary Completion Date : | May 11, 2020 |
| Actual Study Completion Date : | October 6, 2021 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: ccRCC KPS ≥ 70%
Clear-Cell Renal Cell Carcinoma (ccRCC) with Karnofsky Performance Status (KPS) ≥ 70%
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Drug: Nivolumab
Specified dose on specified day
Other Names:
Drug: Ipilimumab Specified Dose on Specified Day
Other Names:
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Experimental: Non-ccRCC, KPS ≥ 70%
Non Clear-Cell Renal Cell Carcinoma (nccRCC) with KPS ≥ 70%
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Drug: Nivolumab
Specified dose on specified day
Other Names:
Drug: Ipilimumab Specified Dose on Specified Day
Other Names:
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Experimental: RCC with non-active Brain Mets, KPS ≥70%
Renal Cell Carcinoma (RCC) with non-active Brain Metastases, with KPS ≥70%
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Drug: Nivolumab
Specified dose on specified day
Other Names:
Drug: Ipilimumab Specified Dose on Specified Day
Other Names:
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Experimental: any RCC with KPS 50%-60%
Renal Cell Carcinoma (RCC), regardless of any histology or existing non-active brain metastasis, with KPS 50%-60%
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Drug: Nivolumab
Specified dose on specified day
Other Names:
Drug: Ipilimumab Specified Dose on Specified Day
Other Names:
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Primary Outcome Measures :
- Number of Participants With High Grade (Grade 3-4) Immune Mediated Adverse Events (IMAEs) [ Time Frame: Approximately 39 Months ]Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity
- Number of Participants With High Grade (Grade 5) Immune Mediated Adverse Events (IMAEs) [ Time Frame: Approximately 39 Months ]Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity
Secondary Outcome Measures :
- Time to Onset of Grade 3-5 Immune Mediated Adverse Events (IMAEs) [ Time Frame: From first dose to the earliest IMAE (grade 3-5) event onset date (up to approximately 116 weeks) ]Time to onset is defined as the duration of time in weeks from the first dosing to the immune modulating adverse event onset date. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
- Time to Resolution of Grade 3-5 Immune Mediated Adverse Events (IMAEs) [ Time Frame: From the IMAE onset date to the IMAE end date, up to approximately 194 weeks ]Time to resolution is defined as the longest time from IMAE onset date to complete resolution or improvement to the grade at baseline experienced by the participant (the IMAE end date). Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
- Number of Participants Who Received Immune Modulating Medication for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) [ Time Frame: From first dose up to 100 days post last dose (up to approximately 29 months) ]The number of participants who received immune modulating medication for participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
- Number of Participants Who Received Hormone Replacement Therapy for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) [ Time Frame: From first dose up to 100 days post last dose (up to approximately 29 months) ]The number of participants who received Hormone Replacement Therapy for experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
- Number of Participants Who Received ≥ 40mg of Prednisone for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) [ Time Frame: From first dose up to 100 days post last dose (up to approximately 29 months) ]The number of participants who received ≥ 40mg of prednisone for high grade (grades 3-5) IMAEs. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
- Median Progression Free Survival (PFS) [ Time Frame: From first dose to the date of the first documented progressive disease, up to approximately 12 months ]PFS is defined as the time from first dose to the date of the first documented progressive disease (PD) as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause whichever occur first. Progressive disease is defined as progression of existing non-target lesions or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
- Objective Response Rate (ORR) [ Time Frame: From first dose up to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 26 months) ]ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).
- Time to Response Rate (TRR) [ Time Frame: From the date of first dose to first documented CR or PR, up to approximately 15 months ]TTR is defined as the median percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).
- Duration of Response (DOR) [ Time Frame: From first confirmed response to the date of the first documented tumor progression or death, up to approximately 48 months ]DOR is defined as the time between the date of first confirmed response to the date of the first documented tumor progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause, whichever occurs first. DOR will be computed for participants who achieve partial response (PR) or complete response (CR) only. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
1. Type of Participant and Target Disease Characteristics
- Advanced or metastatic RCC
- Histologically confirmed, previously untreated (treatment-naive) RCC
- No prior systemic therapy for RCC except for one prior adjuvant or neoadjuvant therapy for completely resectable RCC
- Measurable disease as per RECIST 1.1. Subject must have extracranial metastasis as measurable disease
- Karnofsky Performance Status (KPS) of at least 70% for Cohort 1, 2, and 3; KPS of 50-60% for Cohort 4
- Tumor tissue need be received by the central vendor (block or unstained slides). Note: Fine Needle Aspiration (FNA)and bone metastases samples are not acceptable for submission.
Exclusion Criteria:
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Medical Conditions
- Subjects with any active autoimmune disease or a history of known autoimmune disease
- Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
- Known HIV or AIDS-related illness
- Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.
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Prior/Concomitant Therapy
- Prior systemic treatment in the metastatic setting with Vascular epithelial growth factor(VEGF) or VEGF receptor targeted therapy
- Prior treatment with an anti-Programmed Death (PD) -1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation 137 (CD137), or anti-cytotoxic T-lymphocyte-associated antigen 4(CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. This includes the utilization of these agents in the neo-adjuvant or adjuvant setting.
- Anti-cancer therapy less than 28 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug.
Other protocol defined inclusion/exclusion criteria 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 ClinicalTrials.gov identifier (NCT number): NCT02982954
Locations
Show 61 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Study Documents (Full-Text)
Documents provided by Bristol-Myers Squibb:
Documents provided by Bristol-Myers Squibb:
Study Protocol [PDF] December 18, 2019
Statistical Analysis Plan [PDF] May 26, 2020
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT02982954 |
| Other Study ID Numbers: |
CA209-920 |
| First Posted: | December 6, 2016 Key Record Dates |
| Results First Posted: | October 14, 2021 |
| Last Update Posted: | November 1, 2022 |
| Last Verified: | October 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma, Renal Cell Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases |
Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Kidney Diseases Urologic Diseases Male Urogenital Diseases Nivolumab Ipilimumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |