An Investigational Immuno-therapy Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Participants With Previously Treated Cancer of the Colon or Rectum That Has Spread (CheckMate 9N9)

Bristol-Myers Squibb (BMS)

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Colorectal Carcinoma; Colorectal Neoplasm; Colorectal Tumors; Colorectal Cancer

Treatments: Drug: Regorafenib; Drug: Trametinib; Biological: Nivolumab; Biological: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03377361

2017-001830-24 (EudraCT Number)

CA209-9N9

Details and patient eligibility

About

The purpose of this study is to investigate treatment with nivolumab in combination with trametinib with or without ipilimumab in participants with previously treated cancer of the colon or rectum that has spread.

Enrollment: 325 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed previously treated metastatic colorectal cancer with adenocarcinoma histology and in Stage IV per American Joint Committee on Cancer (version 4.0) at study entry
• Microsatellite status should be performed per local standard of practice, immunohistochemistry (IHC) and/or PCR. If IHC results are equivocal, PCR is required for determining microsatellite stable (MSS) status
• Must have measurable disease per RECIST 1.1. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 at screening and on cycle 1 day 1 (C1D1)

Exclusion criteria

• BRAF V600 mutant colorectal cancer
• Active brain metastases or leptomeningeal metastases
• Active, known or suspected autoimmune disease
• Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration
• History of interstitial lung disease or pneumonitis
• Prior treatment with immune checkpoint inhibitors and mitogen-activated protein kinase enzymes (MEK) inhibitors
• History of allergy or hypersensitivity to study drug components

Other protocol defined inclusion/exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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325 participants in 6 patient groups

Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib

Experimental group

Treatment:

Biological: Nivolumab

Drug: Trametinib

Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib

Experimental group

Treatment:

Biological: Ipilimumab

Biological: Nivolumab

Drug: Trametinib

Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib

Experimental group

Treatment:

Biological: Ipilimumab

Biological: Nivolumab

Drug: Trametinib

Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib

Experimental group

Treatment:

Biological: Ipilimumab

Biological: Nivolumab

Drug: Trametinib

Part 2 Cohort 5 (3L): Regorafenib

Experimental group

Treatment:

Drug: Regorafenib

Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib

Experimental group

Treatment:

Biological: Ipilimumab

Biological: Nivolumab

Drug: Trametinib