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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 : April 20, 2023
Sponsor:
Collaborators:
Merck Sharp & Dohme LLC
Merck KGaA, Darmstadt, Germany
Eli Lilly and Company
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 19, 2022
First Posted Date  ICMJE February 1, 2022
Last Update Posted Date April 20, 2023
Actual Study Start Date  ICMJE July 11, 2022
Estimated Primary Completion Date March 28, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2022)		 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:
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2022)
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Metastatic Colorectal Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Arm A: encorafenib, cetuximab and pembrolizumab
    Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
    Interventions:
    • Drug: Encorafenib
    • Biological: Cetuximab
    • Biological: Pembrolizumab
  • Active Comparator: Arm B: pembrolizumab
    Participants receive pembrolizumab IV.
    Intervention: Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 19, 2022)		 104
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 28, 2027
Estimated Primary Completion Date March 28, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Czechia,   Denmark,   France,   Germany,   Italy,   Netherlands,   Norway,   Poland,   Slovakia,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05217446
Other Study ID Numbers  ICMJE C4221022
2021-003715-26 ( EudraCT Number )
SEAMARK ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Current Responsible Party Pfizer
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Pfizer
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Merck Sharp & Dohme LLC
  • Merck KGaA, Darmstadt, Germany
  • Eli Lilly and Company
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP