MK-3475-06C/​KEYMAKER-U06 - A Phase 1/2 Open-Label, Umbrella Platform Design Study of MK-2870 With Pembrolizumab (MK-3475) and Chemotherapy in Participants With 1L Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, and Esophageal Adenocarcinoma): Substudy 06C

Studio Clinico

Patologia: Neoplasie dello stomaco, Tumori dell’esofago

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: 1, II

Linee di trattamento: Prima linea

Criteri di inclusione: 

The main inclusion criteria include but are not limited to the following:

- Has histologically and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic 1L gastroesophageal adenocarcinoma
- Is not expected to require tumor resection during the treatment course- Has not had prior systemic therapy administered in the recurrent or metastatic setting
- Has gastroesophageal adenocarcinoma that is not human epidermal growth factor receptor 2 (HER2)/neu positive
- Has provided an archival tumor tissue sample or most recently obtained core, or incisional, or excisional biopsy for a tumor lesion
- Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to \<Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible
- Has adequate organ function
- Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment and verified by blind independent review committee (BICR)
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 3 days before allocation/randomization.
- Has a life expectancy of at least 6 months
- Who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
- Who has history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
- Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART).

Criteri di esclusione: 

The main exclusion criteria include but are not limited to the following:

- Has squamous cell or undifferentiated gastroesophageal cancer.
- Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ/esophageal adenocarcinoma
- Has experienced weight loss \>20% over 3 months before the first dose of study intervention
- Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
- Has Grade \>2 peripheral neuropathy
- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months preceding study intervention
- Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC)
- Has received prior treatment with a topoisomerase I inhibitor-based ADC and/or a topoisomerase I inhibitor-based chemotherapy
- Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
- Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)
- Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- Has received a strong inducer/inhibitor of CYP3A4 that cannot be discontinued
- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has Severe hypersensitivity (≥Grade 3) to pembrolizumab, sacituzumab tirumotecan, or other biologic therapy, chemotherapy (ie, oxaliplatin, fluorouracil, capecitabine), leucovorin, levoleucovorin, or any of their excipients
- Has active autoimmune disease that has required systemic treatment in the past 2 years
- Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has concurrent active hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-hepatitis C virus \[HCV\] Ab positive and detectable HCV ribonucleic acid \[RNA\] infection
- Has GI obstruction, poor oral intake, or difficulty in taking oral medication
- Has poorly controlled diarrhea
- Has had a major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention
- Has history of allogeneic tissue/solid organ transplant
- Have not adequately recovered from major surgery or have ongoing surgical complications.

Trattamento sperimentale: 

Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

Trattamento di controllo: 

Pembrolizumab plus Chemotherapy

Centri partecipanti

Nord Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2023-509307-33

Data di inserimento: 23.12.2024

Promotore

Merck Sharp & Dohme LLC

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na