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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05217446




Registration number
NCT05217446
Ethics application status
Date submitted
19/01/2022
Date registered
1/02/2022
Date last updated
30/04/2024

Titles & IDs
Public title
A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
Scientific 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
Secondary ID [1] 0 0
2021-003715-26
Secondary ID [2] 0 0
C4221022
Universal Trial Number (UTN)
Trial acronym
SEAMARK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Encorafenib
Other interventions - Cetuximab
Other interventions - Pembrolizumab

Experimental: Arm A: encorafenib, cetuximab and pembrolizumab - Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.

Active Comparator: Arm B: pembrolizumab - Participants receive pembrolizumab IV.


Treatment: Drugs: Encorafenib
capsule

Other interventions: Cetuximab
IV

Other interventions: Pembrolizumab
IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Duration of study, approximately 45 months
Secondary outcome [1] 0 0
Incidence of adverse events
Timepoint [1] 0 0
Duration of study, approximately 45 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Duration of study, approximately 45 months
Secondary outcome [3] 0 0
Objective Response (OR)
Timepoint [3] 0 0
Duration of study, approximately 45 months

Eligibility
Key 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
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/03/2027
Actual
Sample size
Target
104
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
GenesisCare North Shore - St Leonards
Recruitment hospital [3] 0 0
Gallipoli Medical Research Foundation - Brisbane
Recruitment hospital [4] 0 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [5] 0 0
Austin Health - Heidelberg
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [7] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4120 - Brisbane
Recruitment postcode(s) [4] 0 0
4120 - Greenslopes
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Belgium
State/province [9] 0 0
Antwerpen
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles-capitale, Région DE
Country [11] 0 0
Belgium
State/province [11] 0 0
Oost-vlaanderen
Country [12] 0 0
Belgium
State/province [12] 0 0
Vlaams-brabant
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Canada
State/province [15] 0 0
Saskatchewan
Country [16] 0 0
Czechia
State/province [16] 0 0
Hradec Králové
Country [17] 0 0
Czechia
State/province [17] 0 0
Olomoucký KRAJ
Country [18] 0 0
Czechia
State/province [18] 0 0
Praha 4
Country [19] 0 0
Czechia
State/province [19] 0 0
Praha 8
Country [20] 0 0
Denmark
State/province [20] 0 0
Hovedstaden
Country [21] 0 0
Denmark
State/province [21] 0 0
Nordjylland
Country [22] 0 0
Denmark
State/province [22] 0 0
Syddanmark
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Clermont Ferrand
Country [25] 0 0
France
State/province [25] 0 0
Clermont-Ferrand
Country [26] 0 0
France
State/province [26] 0 0
Montpellier Cedex 5
Country [27] 0 0
France
State/province [27] 0 0
Montpellier
Country [28] 0 0
Germany
State/province [28] 0 0
Bayern
Country [29] 0 0
Germany
State/province [29] 0 0
Hessen
Country [30] 0 0
Germany
State/province [30] 0 0
Niedersachsen
Country [31] 0 0
Germany
State/province [31] 0 0
Sachsen-anhalt
Country [32] 0 0
Germany
State/province [32] 0 0
Sachsen
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Halle /Saale
Country [35] 0 0
Germany
State/province [35] 0 0
Hamburg
Country [36] 0 0
Italy
State/province [36] 0 0
Cagliari
Country [37] 0 0
Italy
State/province [37] 0 0
Campania
Country [38] 0 0
Italy
State/province [38] 0 0
Emilia-romagna
Country [39] 0 0
Italy
State/province [39] 0 0
Foggia
Country [40] 0 0
Italy
State/province [40] 0 0
Milano
Country [41] 0 0
Italy
State/province [41] 0 0
Torino
Country [42] 0 0
Italy
State/province [42] 0 0
Toscana
Country [43] 0 0
Italy
State/province [43] 0 0
Veneto
Country [44] 0 0
Italy
State/province [44] 0 0
Brescia
Country [45] 0 0
Italy
State/province [45] 0 0
Reggio Emilia
Country [46] 0 0
Netherlands
State/province [46] 0 0
Limburg
Country [47] 0 0
Netherlands
State/province [47] 0 0
Zuid-holland
Country [48] 0 0
Norway
State/province [48] 0 0
Sør-trøndelag
Country [49] 0 0
Norway
State/province [49] 0 0
Oslo
Country [50] 0 0
Poland
State/province [50] 0 0
Wielkopolskie
Country [51] 0 0
Poland
State/province [51] 0 0
Brzozow
Country [52] 0 0
Poland
State/province [52] 0 0
Bytom
Country [53] 0 0
Poland
State/province [53] 0 0
Gdansk
Country [54] 0 0
Poland
State/province [54] 0 0
Radom
Country [55] 0 0
Slovakia
State/province [55] 0 0
Banska Bystrica
Country [56] 0 0
Slovakia
State/province [56] 0 0
Bratislava
Country [57] 0 0
Slovakia
State/province [57] 0 0
Kosice
Country [58] 0 0
Spain
State/province [58] 0 0
A Coruña [LA Coruña]
Country [59] 0 0
Spain
State/province [59] 0 0
Alicante
Country [60] 0 0
Spain
State/province [60] 0 0
Barcelona [barcelona]
Country [61] 0 0
Spain
State/province [61] 0 0
Catalunya [cataluña]
Country [62] 0 0
Spain
State/province [62] 0 0
Madrid, Comunidad DE
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Spain
State/province [64] 0 0
Sevilla
Country [65] 0 0
Spain
State/province [65] 0 0
Valencia
Country [66] 0 0
Spain
State/province [66] 0 0
Zaragoza
Country [67] 0 0
Sweden
State/province [67] 0 0
Stockholms LÄN [se-01]
Country [68] 0 0
Sweden
State/province [68] 0 0
Skövde
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Aberdeen CITY
Country [70] 0 0
United Kingdom
State/province [70] 0 0
England
Country [71] 0 0
United Kingdom
State/province [71] 0 0
London, CITY OF
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Merck KGaA, Darmstadt, Germany
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Eli Lilly and Company
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05217446
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05217446