Metastatic colorectal cancer MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Opdivo (100 mg/10 ml)
Product Name: NIVOLUMAB - 10mL vial - commercial
Product Code: [BMS-936558]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: nivolumab
Sponsors
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 18, signed written informed consent • Histological or cytological confirmed diagnosis of previously treated mCRC with adenocarcinoma histology and in Stage IV per AJCC • Confirmed microsatellite status: only participants with pMMR/MSS mCRC are eligible • Verified KRAS, NRAS (extended RAS) and BRAF mutation status: BRAF V600 mutant are not eligible • Measurable disease per RECIST 1.1 • Provide Tumor Tissue sample at screening. • ECOG Performance Status of 0-1 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 107
Exclusion criteria
Exclusion criteria: 1) Target Disease Exceptions a) Participants with BRAF V600 mutant colorectal cancer are NOT eligible for this study in Part 1, 1A, and 1B only. 2) Medical History and Concurrent Diseases a) Any serious or uncontrolled medical disorder. b) Prior malignancy active within the previous 3 years c) Participants with an active, known or suspected autoimmune disease. d) Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. e) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. f) All toxicities attributed to prior anti-cancer therapy g) Toxicities from the prior anti-cancer treatment have not been resolved to Grade 1 h) Current use of a prohibited medication. i) Prior treatment with any MEK inhibitor j) History of interstitial lung disease or pneumonitis. k) Inability to take oral medication l) Psychological, familial, or sociological condition potentially hampering compliance with the study protocol. m) Additional criteria for Part 2 only: i) Prior treatment with regorafenib or TAS-102 ii) Severe hepatic impairment (Child-Pugh C) iii) Any evidence of active bleeding iv) Prior or current gastrointestinal perforation or fistula v) Arterial or venous thrombotic or embolic events within 6 months before the start of study medication vi) Non-healing wound, non-healing ulcer, or non-healing bone fracture vii) Active infection 3) Physical and Laboratory Test Findings 4) Allergies/Adverse Drug Reaction 5) Other Exclusion Criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Parts 1, and 1A (no EU subjects): - To characterize the safety and tolerability of combination therapies - To establish recommended dosing regimen for the combination (nivolumab plus ipilimumab plus trametinib OR nivolumab plus trametinib) Parts 1B and 2: - To evaluate the ORR in all participants treated with nivolumab plus ipilimumab and trametinib in the 2L and 3L setting (Parts 1B and 2) and regorafenib in 3L (Part 2 only);Secondary Objective: Parts 1, and 1A (no EU subjects): - To evaluate preliminary efficacy Parts 1B and 2: - To evaluate efficacy in all participants treated with nivolumab plus ipilimumab and trametinib in the 2L and 3L setting (Parts 1B and 2); and regorafenib in 3L (Part 2 only) - To evaluate efficacy in subgroups of CMS in 3L MSS CRC patients treated with nivolumab plus ipilimumab and trametinib vs. regorafenib (Part 2), as well as explore efficacy in relation to CMS subgroups in 2L MSS CRC patients (Part 1B) - To characterize the safety and tolerability of combination therapies ;Primary end point(s): ORR by investigator;Timepoint(s) of evaluation of this end point: Under current accrual assumption, approximately 12 months from the FPFT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): BOR, DCR, DOR, TTR, and PFS by investigator, OS and Safety;Timepoint(s) of evaluation of this end point: Under current accrual assumption, approximately 19 months from the FPFT. | — |
Countries
Australia, Belgium, Canada, Czech Republic, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactGSM-CT
Bristol-Myers Squibb International Corporation
Outcome results
None listed