A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator's Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC) (CheckMate 8HW)

Bristol-Myers Squibb (BMS)

Status and phase: Active, not recruiting; Phase 3

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Fluorouracil; Drug: Leucovorin; Drug: Cetuximab; Biological: Ipilimumab; Drug: Oxaliplatin; Biological: Nivolumab; Drug: Irinotecan; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04008030

2018-000040-26 (EudraCT Number)

CA209-8HW

Details and patient eligibility

About

The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS), achieved by nivolumab in combination with ipilimumab or by nivolumab monotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC). This study will also compare nivolumab plus ipilimumab combination vs chemotherapy for treatment of MSI-H/dMMR mCRC participants.

Enrollment: 839 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed recurrent or metastatic colorectal cancer (CRC) irrespective of prior treatment history with chemotherapy and/or targeted agents not amenable to surgery (Applicable only during Part 1 enrollment of the study)
• Histologically confirmed recurrent or metastatic CRC with no prior treatment history with chemotherapy and/or targeted agents for metastatic disease and not amenable to surgery (Applicable during Part 2 enrollment of the study)
• Known tumor microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status per local standard of practice
• Eastern cooperative oncology group (ECOG) performance status lower than or equal to 1

Exclusion criteria

• An active, known or suspected autoimmune disease
• History of interstitial lung disease or pneumonitis
• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

Other protocol-defined inclusion/exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

839 participants in 3 patient groups

Arm A: Nivolumab Monotherapy

Experimental group

Treatment:

Biological: Nivolumab

Arm B: Nivolumab + Ipilimumab Combination

Experimental group

Treatment:

Biological: Nivolumab

Biological: Ipilimumab

Arm C: Investigator's Choice Chemotherapy

Active Comparator group

Description:

Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress

Treatment:

Drug: Bevacizumab

Drug: Irinotecan

Drug: Oxaliplatin

Drug: Cetuximab

Drug: Leucovorin

Drug: Fluorouracil