C4221022 - SEAMARK - 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

Studio Clinico

Patologia: Tumori del colon retto

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: II Randomizzato

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Male or female participants ≥ 16 Years
- 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.

Criteri di esclusione: 

- 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).

Numero di pazienti previsti: 

20

Schema di trattamento: 

Arm A: encorafenib orally + cetuximab IV + pembrolizumab IV
Arm B: pembrolizumab IV

Trattamento sperimentale: 

encorafenib orally + cetuximab IV + pembrolizumab IV

Trattamento di controllo: 

pembrolizumab IV

Obiettivi primari dello studio: 

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

Obiettivi secondari dello studio: 

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).

Data di inizio dell'arruolamento: 25.07.2022

Data di fine dell'arruolamento: 24.05.2024

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2021-003715-26

Data di inserimento: 29.09.2022

Data di aggiornamento: 03.11.2023

Promotore

Pfizer

CRO

PPD

Principal Investigator ITALIA

IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo (FG)

Riferimento: Dr. Evaristo Maiello

Telefono: 0882412792

Email: e.maiello@operapadrepio.it

Localita: San Giovanni Rotondo (FG)