Metastatic Colorectal Cancer
Conditions
Keywords
Keynote-D31, BRAF V600E mutation positive, Colon cancer, Rectal cancer, Metastatic colon cancer, Colon cancer BRAF, Rectal cancer BRAF, MSI-H colorectal cancer, MSI-H colon cancer
Brief summary
The purpose of this study is to learn about the effects of three study medicines (encorafenib, cetuximab, and pembrolizumab) given together for the treatment of colorectal cancer that: * is metastatic (spread to other parts of the body); * has the condition of genetic hypermutability (tendency to mutation) or impaired DNA mismatch repair (MMR) * has a certain type of abnormal gene called "BRAF" and; * has not received prior treatment. All participants in this study will receive pembrolizumab at the study clinic as an intravenous (IV) infusion (given directly into a vein) at the study clinic. In addition, half of the participants will take encorafenib by mouth at home every day and cetuximab by IV infusion at the study clinic. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
Interventions
DRUGEncorafenib
capsule
BIOLOGICALCetuximab
IV
BIOLOGICALPembrolizumab
IV
Sponsors
Pfizer
Merck Sharp & Dohme LLC
Merck KGaA, Darmstadt, Germany
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label, multicenter study of encorafenib and cetuximab plus pembrolizumab (Triplet Arm \[Arm A\]) versus pembrolizumab alone (Control Arm \[Arm B\]) as first-line treatment in participants with BRAF inhibitor (BRAF) V600E-mutant and microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) mCRC. Randomization will be stratified by ECOG (0 vs 1)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Have not received prior systemic regimens for metastatic disease. * Measurable disease per RECIST 1.1 * Adequate organ function
Exclusion criteria
* Colorectal adenocarcinoma that is RAS mutant or for which RAS mutation status is unknown * Known active central nervous system metastases and/or carcinomatous meningitis; leptomeningeal disease * Immunodeficiency or active autoimmune disease requiring systemic treatment in the past 2 years * Presence of acute or chronic pancreatitis * Clinically significant cardiovascular diseases (eg, thromboembolic or cerebrovascular accident events ≤ 12 wks prior) * Received a live or live-attenuated vaccine within 30 days of planned start of study medication * 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). * 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Duration of study, approximately 45 months | PFS per investigator, defined as the time from randomization until PD based on investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first: |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Duration of study, approximately 45 months | Incidence and severity of AEs graded according to the NCI CTCAE v4.03: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B) |
| Overall Survival (OS) | Duration of study, approximately 45 months | OS is defined as the time from the date of randomization to the date of death due to any cause: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B) |
| Objective Response (OR) | Duration of study, approximately 45 months | OR is defined as a CR or PR per RECIST version 1.1 recorded from the date of randomization until date of first documentation of PD, death, or start of new anti-cancer therapy: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B) |
Countries
Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Italy, Netherlands, Norway, Poland, Slovakia, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed