Metastatic Colorectal CancerPhase 2SEAMARKNCT05217446
A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
A Phase 2 study testing Encorafenib, Cetuximab and Pembrolizumab in people with Metastatic Colorectal Cancer, run by Pfizer at 59 sites in 15 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Encorafenib, Cetuximab and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 59 sitesin 15 countries
- Study dates
- 11 Jul 2022to 26 Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
59 sites in 15 countries.
59 sites in 15 countries
Italy12 sites
Fondazione Poliambulanza Istituto Ospedaliero
Brescia, 25124
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
Candiolo, Torino, 10060
Ospedale di Guastalla
Guastalla, Emilia-Romagna, 42016
Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno
Livorno, Tuscany, 57124
ASST Grande Ospedale Metropolitano Niguarda
Milan, Milano, 20162
Istituto Europeo di Oncologia IRCCS
Milan, 20141
Policlinico Universitario Monserrato
Monserrato, Cagliari, 09042
Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli
Naples, Campania, 80131
Istituto Oncologico Veneto IRCCS
Padova, Veneto, 35128
Azienda Ospedaliero Universitaria Pisana
Pisa, Tuscany, 56126
Arcispedale Santa Maria Nuova
Reggio Emilia, 42123
IRCCS Casa Sollievo della Sofferenza
San Giovanni Rotondo, Foggia, 71013
Spain9 sites
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], 08035
Hospital Clínic de Barcelona
Barcelona, Catalunya [cataluña], 08036
Institut Català d'Oncologia - L'Hospitalet
L'Hospitalet de Llobregat, Catalunya [cataluña], 08908
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Comunidad de, 28034
Hospital General Universitario Gregorio Marañon
Madrid, 28007
CHUS - Hospital Clinico Universitario
Santiago de Compostela, A Coruña [LA Coruña], 15706
Hospital Universitario Virgen Del Rocio
Seville, 41013
Hospital General Universitario de Valencia
Valencia, 46014
Hospital Universitario Miguel Servet
Zaragoza, 50009
United States6 sites
The West Clinic, PLLC dba West Cancer Center
Germantown, Tennessee, 38138
MD Anderson Cancer Center
Houston, Texas, 77030
Mount Sinai Cancer Center
Miami Beach, Florida, 33140
Mayo Clinic Building - Phoenix
Phoenix, Arizona, 85054
Mayo Clinic Hospital
Phoenix, Arizona, 85054
Mayo Clinic
Scottsdale, Arizona, 85259
Denmark5 sites
Aalborg Universitetshospital, Syd
Aalborg, North Denmark, 9000
Herlev and Gentofte Hospital
Copenhagen, Capital Region, 2730
Rigshospitalet
Copenhagen, Capital, 2100
Vejle Hospital, Department of Oncology
Vejle, Region Syddanmark, 7100
Vejle Sygehus
Vejle, Region Syddanmark, 7100
France5 sites
Centre Hospitalier Universitaire Estaing
Clermont-Ferrand, 63100
CHU Estaing
Clermont-Ferrand, 63100
Institut Regional du Cancer de Montpellier - ICM Val d'Aurelle
Montpellier, 34298
Hôpital Européen Georges Pompidou
Paris, Paris, 75015
Hôpital Saint Antoine
Paris, 75571
Canada4 sites
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
Saskatchewan Health Authority
Saskatoon, Saskatchewan, S7K 0M7
Saskatoon Cancer Center
Saskatoon, Saskatchewan, S7N4H4
Sunnybrook Health Sciences - Odette Cancer Centre
Toronto, Ontario, M4N 3M5
Australia3 sites
Austin Health
Heidelberg, Victoria, 3084
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Royal Melbourne Hospital
Parkville, Victoria, 3000
Belgium3 sites
Institut Jules Bordet
Anderlecht, Bruxelles-capitale, Région de, 1070
Imelda General Hospital
Bonheiden, Antwerpen, 2820
Cliniques universitaires Saint-Luc
Brussels, Bruxelles-capitale, Région de, 1200
Czechia3 sites
Fakultni nemocnice Hradec Kralove
Hradec Králové, Hradec Králové, 500 05
Fakultni Thomayerova nemocnice
Prague, Praha 4, 14059
Fakultni nemocnice Bulovka
Prague, Praha 8, 180 81
Germany2 sites
Facharztzentrum Eppendorf
Hamburg, 20249
Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
Munich, Bavaria, 81737
Poland2 sites
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza
Brzozów, 36-200
Przychodnia Lekarska KOMED
Konin, Greater Poland Voivodeship, 62-500
United Kingdom2 sites
Aberdeen Royal Infirmary
Aberdeen, Aberdeen CITY, AB25 2ZN
Heartlands Hospital
Birmingham, B9 5SS
About this study
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
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.
Read more
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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Encorafenib, Cetuximab, Pembrolizumab
- 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
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EncorafenibDrug
Also called PF-07263896 LGX818 ONO-7702 W0090
capsule
CetuximabBiological
Also called Erbitux
IV
PembrolizumabBiological
Also called Keytruda®, MK-3475
IV
| Study group | Role | What they receive |
|---|---|---|
| Arm B: pembrolizumab | Active comparator | Participants receive pembrolizumab IV. Receives: Biological: Pembrolizumab |
| Arm A: encorafenib, cetuximab and pembrolizumab | Experimental | Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV. Receives: Drug: Encorafenib; Biological: Cetuximab; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
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:
Measured: Duration of study, approximately 45 months
Secondary outcomes (3)
Incidence of adverse events
Incidence and severity of AEs graded according to the NCI CTCAE v4.03: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B)
Measured: Duration of study, approximately 45 months
Overall Survival (OS)
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)
Measured: Duration of study, approximately 45 months
Objective Response (OR)
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)
Measured: Duration of study, approximately 45 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2022
- Study start11 Jul 2022
- Primary completion19 Jun 2026
- Study completion26 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC, Merck KGaA, Darmstadt, Germany, Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05217446
- Sponsor's protocol ID
- C4221022
- Other IDs
- SEAMARK, 2024-512119-34-00, MK-3475-D31, KEYNOTE-D31
- Acronym
- SEAMARK
- Status last verified
- Jul 2026
- First submitted
- 19 Jan 2022
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Elez E, Kopetz S, Tabernero J, Bekaii-Saab T, Taieb J, Yoshino T, Manji G, Fernandez K, Abbattista A, Zhang X, Morris VK. SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAFV600E-mutant mCRC. Future Oncol. 2024 Apr;20(11):653-663. doi: 10.2217/fon-2022-1249. Epub 2023 Oct 10.
PubMed 37815847
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05217446
- Acronym / sponsor ID
- SEAMARK / C4221022
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Keynote-D31, BRAF V600E mutation positive, Colon cancer, Rectal cancer, Metastatic colon cancer, Colon cancer BRAF, Rectal cancer BRAF, MSI-H colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 108 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC, Merck KGaA, Darmstadt, Germany, Eli Lilly and Company
- Study start
- 11 Jul 2022 (actual)
- Primary completion
- 19 Jun 2026 (actual)
- Study completion
- 26 Jan 2027 (estimated)
- First posted
- 1 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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)
| Arm | Type | Receives |
|---|---|---|
| Arm B: pembrolizumab | Active comparator | Biological: PembrolizumabParticipants receive pembrolizumab IV. |
| Arm A: encorafenib, cetuximab and pembrolizumab | Experimental | Drug: Encorafenib, Biological: Cetuximab, Biological: PembrolizumabParticipants receive encorafenib orally + cetuximab IV + pembrolizumab IV. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EncorafenibAlso: PF-07263896 LGX818 ONO-7702 W0090capsule | Drug | Arm A: encorafenib, cetuximab and pembrolizumab |
| CetuximabAlso: ErbituxIV | Biological | Arm A: encorafenib, cetuximab and pembrolizumab |
| PembrolizumabAlso: Keytruda®, MK-3475IV | Biological | Arm A: encorafenib, cetuximab and pembrolizumab, Arm B: pembrolizumab |
Primary outcome
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:
3 secondary outcomes
Incidence of adverse events
Time frame: Duration of study, approximately 45 months
Overall Survival (OS)
Time frame: Duration of study, approximately 45 months
Objective Response (OR)
Time frame: Duration of study, approximately 45 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Derived from this study: PubMed 37815847Elez E, Kopetz S, Tabernero J, Bekaii-Saab T, Taieb J, Yoshino T, Manji G, Fernandez K, Abbattista A, Zhang X, Morris VK. SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAFV600E-mutant mCRC. Future Oncol. 2024 Apr;20(11):653-663. doi: 10.2217/fon-2022-1249. Epub 2023 Oct 10.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
59 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Encorafenib, Cetuximab and Pembrolizumab in people with Metastatic Colorectal Cancer, run by Pfizer at 59 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in Italy, Spain, United States, Denmark, France and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: Duration of study, approximately 45 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05217446, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.