H.E.C.T.O.R. - MK-1308A-008

Essai clinique

Type :	Industriel
Statut :	Ouvert
Phase :	II
Date d'ouverture :	25/06/2021
Date clôture :	30/08/2025
Promoteur :	Merck Sharp & Dohme LLC
Progression du cancer:	Loco-régional

Résumé :

The purpose of this study is to assess the efficacy and safety of co-formulated pembrolizumab/quavonlimab versus other treatments in participants with MSI-H or dMMR Metastatic Stage IV Colorectal Cancer.

Domaines/spécialités :

Cancers digestifs

Colon
Rectum

Pathologies :

Tumeur maligne du côlon - Cim10 : C18
Tumeur maligne du rectum - Cim10 : C20

Liens externes :

Critères de population

Sexe : Homme et femme

Age minimum : 18 ans

Critères d’inclusion :

Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by American Joint Committee on Cancer [AJCC] version 8)
Has locally confirmed dMMR/MSI-H
Has a life expectancy of at least 3 months
Female participants are eligible to participate if not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP), or if a WOCBP then uses a contraceptive method that is highly effective or is abstinent on a long-term and persistent basis, during the intervention period and for at least 120 days after the last dose of study intervention
Has measurable disease per RECIST 1.1 as assessed by the site and verified by BICR
Submit an archival or newly obtained tumor tissue sample that has not been previously irradiated; formalin-fixed, paraffin embedded (FFPE) blocks are preferred to slides.
Has adequate organ function

Cohort A:

- Has been previously treated for their disease and radiographically progressed per RECIST 1.1 on or after or could not tolerate standard treatment, which must include all of the following agents if approved and locally available in the country where the participant is randomized:

Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as equivalent to fluorouracil in prior therapy)
With or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (e.g., bevacizumab)
At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for rat sarcoma viral oncogene homolog (RAS) wild-type participants with left-sided tumors. Prior EGFR therapy is optional for patients with right sided RAS Wild-type (WT) tumors.

Cohort B:

- Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for this disease

Critères d’exclusion :

Has received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor
Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
Has not recovered adequately from a surgery procedure, and/or has any complications from a prior surgery before starting study intervention
Has received prior radiotherapy within 2 weeks of start of study intervention
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has severe hypersensitivity (≥Grade 3) to pembrolizumab, quavonlimab, favezelimab, vibostolimab, MK-4830, and/or any of their excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
Has a history of acute or chronic pancreatitis
Has neuromuscular disorders associated with an elevated creatine kinase
Has urine protein ≥1 gram/24 hours
Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or bacterial infections, etc.)
Has a known history of Human Immunodeficiency Virus (HIV) infection
Has known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) or active Hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected or anti-HCV antibody positive) infection
Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study intervention administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before randomization/allocation
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
Has had an allogenic tissue/solid organ transplant

Centre d'investigation

En cours

Nom :	Centre Georges François Leclerc - CGFL
Ville :	DIJON (21)

RESPONSABLE MÉDICAL

Nom :	Pr GHIRINGHELLI
Prénom :	François
Téléphone :	Non disponible
Email :	fghiringhelli@cgfl.fr

CONTACT TECHNIQUE

Nom :	LEVEQUE
Prénom :	Nathalie
Téléphone :	03 45 34 80 68
Email :	nleveque@cgfl.fr

Référentiels Oncologik

Côlon
Rectum