West Cancer Center

COLORECTAL: METASTATIC: 1ST LINE: BRAF MT: BREAKWATER

An open-label, multicenter, randomized Phase 3 study of first-line encorafenib plus cetuximab with or without chemotherapy versus standard of care therapy with a safety lead-in of encorafenib and cetuximab plus chemotherapy in participants with metastatic BRAF V600E-mutant colorectal cancer

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Malignancy

Colon, Rectum, Colorectal

Stage

Stage 4

Phase

Phase 3

Status

Open to Enrollment

Line Of Therapy

Investigational Agent

Encorafenib, cetuximab

Drug Class

BRAF inhibitor, EGFR antibody

PI

Sponsor

Pfizer

Path

Key Eligibility Criteria Details

Age 16 or greater
Histologically or cytologically confirmed Stage IV CRC
Must contain a BRAF V600E mutation on local (FMI or Caris) or central testing
No prior systemic treatment in metastatic setting
Prior adjuvant or neoadjuvant therapy is OK only if relapse/metastasis is 6 months or greater from the end of the neo/adjuvant treatment
No history of acute or chronic pancreatitis
No symptomatic brain mets
Must have measurable disease

COLON: METASTATIC: BRAFmt: MSI-h: 1st Line: SEAMARK

A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF ENCORAFENIB AND CETUXIMAB PLUS PEMBROLIZUMAB VERSUS PEMBROLIZUMAB ALONE IN PARTICIPANTS WITH PREVIOUSLY UNTREATED BRAF V600E-MUTANT, MSI H/DMMR METASTATIC COLORECTAL CANCER

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Malignancy

Colon cancer, rectal cancer, colorectal cancer

Stage

Stage 4

Phase

Phase 2

Status

Open to Enrollment

Line Of Therapy

1st Line

Investigational Agent

encorafenib, cetuximab, pembrolizumab

Drug Class

BRAF inhibitor, EGFR mAb, PD-1 inhibitor

PI

Brad Somer, MD

Sponsor

Pfizer

Path

BRAF V600 mutant, MSI-h, dMMR

Key Eligibility Criteria Details

Locally confirmed microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) stage IV colorectal carcinoma
Locally confirmed BRAF V600E mutation in tumor tissue or blood
ECOG PS 0 or 1
Have not received prior systemic regimens for metastatic disease.
Measurable disease
RAS wt
No known active central nervous system metastases and/or carcinomatous meningitis; leptomeningeal disease
No immunodeficiency or active autoimmune disease requiring systemic treatment in the past 2 years
No presence of acute or chronic pancreatitis
No previous treatment with any selective BRAF inhibitor (eg, encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) or any epidermal growth factor receptor (EGFR) inhibitor (eg, cetuximab, panitumumab).
No previous treatment with an immune checkpoint inhibitor (eg, anti-programmed cell death [PD-1], anti-PD-L1 or anti-PD-L2 agent); or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).

COLORECTAL: METASTATIC: MSI-h: MK-1308A-008

A Phase 2, Multicenter, Multi Arm, Study to Evaluate MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)

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Malignancy

Colon cancer, rectal cancer, colorectal cancer

Stage

Stage 4

Phase

Phase 2

Status

Open to Enrollment

Line Of Therapy

1st or later

Investigational Agent

pembrolizumab/quavonlimab, pembrolizumab/favezelimab, pembrolizumab/vibostolimab, pembrolizumab+MK-4830

Drug Class

Various immunotherapy combinations

PI

Brad Somer, MD

Sponsor

Merck Sharp and Dohme

Path

Adenocarcinoma, MSI-h, dMMR

Key Eligibility Criteria Details

HIstologically confirmed diagnosis of Stage IV CRC
Locally confirmed dMMR/MSI-H
Life expectancy of at least 3 months
Measurable disease
Cohort A:
- Previously treated with 5-FU, oxaliplatin, irinotecan (and anti-EGFR if KRASwt and left-sided tumor)
Cohort B:
- No prior thearpy for stage IV disease
No prior T-cell directed therapy
No concurrent use of high dose steroids
No known CNS mets
No active autoimmune disease
No known HIV or active HBV/HCV
No clinically significant cardiac disease