MK1308A-008 - A Phase 2, Multicenter, Multi Arm, Study to Evaluate MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer

Studio Clinico

Patologia: Tumori del colon retto

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: II

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Prima/N linee

Criteri di inclusione: 

- 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:
1. Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as equivalent to fluorouracil in prior therapy)
2. With or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (e.g., bevacizumab)
3. 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

Criteri di esclusione: 

- 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

Numero di pazienti previsti: 

320

Schema di trattamento: 

Active Comparator: Pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years
Experimental: Pembrolizumab/Quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years
Experimental: Pembrolizumab/Favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years
Experimental: Pembrolizumab/Vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years
Experimental: Pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years

Trattamento sperimentale: 

Pembrolizumab + Quavonlimab/ Pembrolizumab + Favezelimab /Pembrolizumab + Vibostolimab/ Pembrolizumab + MK4830

Trattamento di controllo: 

Pembrolizumab

Obiettivi primari dello studio: 

Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)

Data di fine dell'arruolamento: 30.11.2023

Centri partecipanti

Nord Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-005114-18

Data di inserimento: 10.05.2022

Promotore

Merck Sharp & Dohme LLC

CRO

/

Principal Investigator ITALIA

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Riferimento: Dr. Antonio Avallone

Telefono: 0815903360

Email: a.avallone@istitutotumori.na.it

Localita: Napoli