Description:
The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination
with other anti-cancer drugs, will result in meaningful tumor size reduction, in patients
with colon cancer that has come back or has spread, and who have a specific biomarker in
their tumors.
Title
- Brief Title: An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread
- Official Title: A Phase 2 Clinical Trial of Nivolumab, or Nivolumab Combinations in Recurrent and Metastatic Microsatellite High (MSI-H) and Non-MSI-H Colon Cancer
Clinical Trial IDs
- ORG STUDY ID:
CA209-142
- SECONDARY ID:
2013-003939-30
- NCT ID:
NCT02060188
Conditions
- Microsatellite Unstable Colorectal Cancer
- Microsatellite Stable Colorectal Cancer
- Mismatch Repair Proficient Colorectal Cancer
- Mismatch Repair Deficient Colorectal Cancer
Interventions
Drug | Synonyms | Arms |
---|
Ipilimumab | Yervoy | Nivolumab (Nivo) + Ipilimumab (Ipi) |
Nivolumab | BMS-936558, Opdivo | Nivolumab (Nivo) + BMS-986016 Cohort C5 |
Cobimetinib | Cotellic | Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib Cohort C4 |
Daratumumab | Darzalex | Nivolumab (Nivo) + Daratumumab Cohort C6 |
anti-LAG-3 antibody | BMS-986016 | Nivolumab (Nivo) + BMS-986016 Cohort C5 |
Purpose
The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination
with other anti-cancer drugs, will result in meaningful tumor size reduction, in patients
with colon cancer that has come back or has spread, and who have a specific biomarker in
their tumors.
Detailed Description
Allocation: The Microsatellite Instability High (MSI-High) and C4 and C6 Cohort Parts of the
trial are Non-randomized, The Non-MSI high Dose Escalation Phase part of the trial contained
a randomized portion
Trial Arms
Name | Type | Description | Interventions |
---|
Nivolumab Monotherapy | Experimental | Nivolumab administered as IV infusion at a dose of 3mg/kg every 2 weeks until disease progression | |
Nivolumab (Nivo) + Ipilimumab (Ipi) | Experimental | Nivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3 week (wk) for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression
Dose Escalation Phase: (Complete)
Dose Level (DL) 1: Nivo 0.3mg/Kg with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression
DL 1: Nivo 1mg/Kg IV with Ipi 1 mg/Kg IV every 3 wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression
DL 2a: Nivo 1mg/Kg IV with Ipi 3 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression
DL 2b: Nivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression | |
Nivolumab (Nivo) + Ipilimumab (Ipi) Cohort C3 | Experimental | Nivo IV dosed every 2wk with Ipi IV dosed every 6wk. | |
Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib Cohort C4 | Experimental | Nivo IV dosed every 2wk, with Ipi IV dosed every 6wk, combined with Cobimetinib dosed orally once daily 21 days on/7 days off. | - Ipilimumab
- Nivolumab
- Cobimetinib
|
Nivolumab (Nivo) + BMS-986016 Cohort C5 | Experimental | Nivo IV dosed every 2wk with BMS-986016 dosed every 2 wk | - Nivolumab
- anti-LAG-3 antibody
|
Nivolumab (Nivo) + Daratumumab Cohort C6 | Experimental | Daratumumab IV dosed weekly for week 1-8; then every 2 wks from Week 9-24; then every 4 wks on week 25; with Nivo dosed every 2 wks starting at week 3 and every 4 wks starting at week 25 | |
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com
Inclusion Criteria:
- Men and women ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Histologically confirmed recurrent or metastatic colorectal cancer
- Measurable disease by CT or MRI
- Testing for MSI Status (by an accredited lab)
1. Subjects with microsatellite instability high (MSI-H) tumors will enroll in the
MSI-H Cohort (mStage and cStage groups), the C3 Cohort, and the C5 Cohort.
2. Subjects with phenotypes that are non-microsatellite instability high (non-MSI-H)
will enroll in the non- MSI-H Safety Cohort and the C6, C4 Cohorts.
- Adequate organ function as defined by study-specific laboratory tests
- Must use acceptable form of birth control throughout the study. After the final dose
of study drug, an acceptable form of birth control must be used for 23 weeks for women
of childbearing potential (WOCBP) and 31 weeks for men who are sexually active with
WOCBP
- Signed informed consent
- Willing and able to comply with study procedures
- Subjects enrolled into the C3 Cohort must have not had treatment for their metastatic
disease
Exclusion Criteria:
- Active brain metastases or leptomeningeal metastases are not allowed.
- Prior treatment with an anti-Programmed Death Receptor (PD)-1, anti-PD-L1, anti-PD-L2,
anti-Cytotoxic T-Cell Lymphoma-4 Antigen (CTLA-4) antibody, or any other antibody or
drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Prior malignancy active within the previous 3 years except for locally curable cancers
- Subjects with active, known or suspected autoimmune disease
- Subjects with a condition requiring systemic treatment with either corticosteroids or
other immunosuppressive medications within 14 days of study drug administration
Other protocol defined inclusion/exclusion criteria could apply
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective response rate (ORR) in all MSI-High and non-MSI-High subjects as determined by Investigators |
Time Frame: | The final analysis of the primary endpoint will occur at least 6 months after the last enrolled subject's first dose of study therapy (Approximately up to 34 months) |
Safety Issue: | |
Description: | (Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later)) (Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later)) |
Secondary Outcome Measures
Measure: | ORR in all MSI-H and non-MSI-H subjects based on IRRC determination |
Time Frame: | The final analysis of the secondary endpoint will occur the time of the primary endpoint analysis (Approximately up to 34 months) |
Safety Issue: | |
Description: | Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/- wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued(whichever occurs later) |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Bristol-Myers Squibb |
Last Updated
November 6, 2019