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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05217446

Collaborator

Merck Sharp & Dohme LLC (Industry), Merck KGaA, Darmstadt, Germany (Industry), Eli Lilly and Company (Industry)

104

Enrollment

Locations

Arms

56.4

Anticipated Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Anticipated 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)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 :

Jul 14, 2022

Anticipated Primary Completion Date :

Mar 28, 2026

Anticipated Study Completion Date :

Mar 28, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: encorafenib, cetuximab and pembrolizumab Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.	Drug: Encorafenib capsule Other Names: PF-07263896 LGX818 ONO-7702 W0090 Biological: Cetuximab IV Other Names: Erbitux Biological: Pembrolizumab IV Other Names: Keytruda, Lambrolizumab b MK-3475
Active Comparator: Arm B: pembrolizumab Participants receive pembrolizumab IV.	Biological: Pembrolizumab IV Other Names: Keytruda, Lambrolizumab b MK-3475

Arm

Intervention/Treatment

Experimental: Arm A: encorafenib, cetuximab and pembrolizumab

Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.

Drug: Encorafenib

capsule

Other Names:

PF-07263896 LGX818 ONO-7702 W0090

Biological: Cetuximab

Other Names:

Erbitux

Biological: Pembrolizumab

Other Names:

Keytruda, Lambrolizumab b MK-3475

Active Comparator: Arm B: pembrolizumab

Participants receive pembrolizumab IV.

Biological: Pembrolizumab

Other Names:

Keytruda, Lambrolizumab b MK-3475

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Cancer Center	Miami Beach	Florida	United States	33140
2	Columbia University Medical Center	New York	New York	United States	10032
3	GenesisCare North Shore	St Leonards	New South Wales	Australia	2065
4	Gallipoli Medical Research Foundation	Brisbane	Queensland	Australia	4120
5	Greenslopes Private Hospital	Greenslopes	Queensland	Australia	4120
6	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
7	Royal Melbourne Hospital	Parkville	Victoria	Australia	3052
8	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia	Italy	71013
9	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino	Italy	10060
10	Przychodnia Lekarska KOMED	Konin	Wielkopolskie	Poland	62-500
11	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza	Brzozow		Poland	36-200
12	SPZOZ Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu	Bytom		Poland	41-902
13	Copernicus Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk		Poland	80-219
14	Fakultna nemocnica s poliklinikou F. D. Roosevelta Banska Bystrica	Banska Bystrica		Slovakia	975 17
15	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [LA Coruña]	Spain	15706
16	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [barcelona]	Spain	08035
17	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad DE	Spain	28034
18	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad DE	Spain	28041
19	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
20	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
21	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
22	Hospital General Universitario de Valencia	Valencia		Spain	46014