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A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer (SEAMARK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05217446
Recruitment Status : Recruiting
First Posted : February 1, 2022
Last Update Posted : June 1, 2023
Sponsor:
Collaborators:
Merck Sharp & Dohme LLC
Merck KGaA, Darmstadt, Germany
Eli Lilly and Company
Information provided by (Responsible Party):
Pfizer

Study Description
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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.


Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Encorafenib Biological: Cetuximab Biological: Pembrolizumab Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
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)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A: encorafenib, cetuximab and pembrolizumab
Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
 Drug: Encorafenib
capsule
Other Name: PF-07263896 LGX818 ONO-7702 W0090

Biological: Cetuximab
IV
Other Name: Erbitux

Biological: Pembrolizumab
IV
Other Name: Keytruda, Lambrolizumab b MK-3475
Active Comparator: Arm B: pembrolizumab
Participants receive pembrolizumab IV.
 Biological: Pembrolizumab
IV
Other Name: Keytruda, Lambrolizumab b MK-3475


Outcome Measures
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Primary Outcome Measures :
  1. 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:


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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Sponsors and Collaborators
Pfizer
Merck Sharp & Dohme LLC
Merck KGaA, Darmstadt, Germany
Eli Lilly and Company
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05217446    
Other Study ID Numbers: C4221022
2021-003715-26 ( EudraCT Number )
SEAMARK ( Other Identifier: Alias Study Number )
First Posted: February 1, 2022    Key Record Dates
Last Update Posted: June 1, 2023
Last Verified: May 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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
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
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
 Intestinal Diseases
Rectal Diseases
Pembrolizumab
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action