A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer (SEAMARK)
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|ClinicalTrials.gov Identifier: NCT05217446|
Recruitment Status : Recruiting
First Posted : February 1, 2022
Last Update Posted : March 20, 2023
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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.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Drug: Encorafenib Biological: Cetuximab Biological: Pembrolizumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||104 participants|
|Intervention Model:||Parallel Assignment|
|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)|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||July 11, 2022|
|Estimated Primary Completion Date :||March 28, 2026|
|Estimated Study Completion Date :||March 28, 2027|
Experimental: Arm A: encorafenib, cetuximab and pembrolizumab
Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
Other Name: PF-07263896 LGX818 ONO-7702 W0090
Other Name: Erbitux
Other Name: Keytruda, Lambrolizumab b MK-3475
Active Comparator: Arm B: pembrolizumab
Participants receive pembrolizumab IV.
Other Name: Keytruda, Lambrolizumab b MK-3475
- Progression-free Survival (PFS) [ Time Frame: 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:
- Incidence of adverse events [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||16 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05217446
|Contact: Pfizer CT.gov Call Center||1-800-718-1021||ClinicalTrials.gov_Inquiries@pfizer.com|
|Study Director:||Pfizer CT.gov Call Center||Pfizer|
|Other Study ID Numbers:||
2021-003715-26 ( EudraCT Number )
SEAMARK ( Other Identifier: Alias Study Number )
|First Posted:||February 1, 2022 Key Record Dates|
|Last Update Posted:||March 20, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
BRAF V600E mutation positive
Metastatic colon cancer
Colon cancer BRAF
Rectal cancer BRAF
MSI-H colorectal cancer
MSI-H colon cancer
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Antineoplastic Agents, Immunological