MK-3475-06E - A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy in Participants With 1L Locally Advanced Unresectable/Metastatic Esophageal Cancer (KEYMAKER-U06 Substudy 06E)

Studio Clinico

Patologia: 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 or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first-line (1L) setting.
- Has measurable disease per RECIST 1.1 as assessed by the local site. investigator/radiology assessment and verified by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
- Has AEs due to previous anticancer therapies of ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable.
- Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
- Participants 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.
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Criteri di esclusione: 

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

- Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer.
- Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula.
- Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention.
- Has clinically significant corneal disease.
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received prior treatment with orlotamab, enoblituzumab, or other humanized anti-B7 homologue 3 (B7-H3)-targeted agents.
- Has received prior treatment with a topoisomerase-I inhibitor, including antibody-drug conjugate (ADC).
- Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.
- 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. Administration of killed vaccines is allowed.
- Has inadequate cardiac function assessed as: - corrected QT interval by Fredericia (QTcF) value >470 msec.
- Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
- Has peripheral neuropathy ≥ Grade 2.
- Has 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 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 active autoimmune disease that has required systemic treatment in the past 2 years.
- Has had (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, and/or suspected interstitial lung disease (ILD)/pneumonitis that cannot be ruled out by imaging at Screening.
- Has active infection requiring systemic therapy.
- Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder.
- Has severe hypersensitivity (≥Grade 3) to treatment with a monoclonal antibody (mAb) or known sensitivity or intolerance to pembrolizumab, I-DXd, study chemotherapy agents and/or to any of their excipients, murine proteins, or platinum containing products.
- Has had allogeneic tissue/solid organ transplant.
- Have not adequately recovered from major surgery or have ongoing surgical complications.
- Are incapacitated.

Trattamento sperimentale: 

Pembrolizumab + I-DXd
Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin
Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin + Oxaliplatin
Pembrolizumab + Sacituzumab tirumotecan + 5-FU IV + Leucovorin or Levoleucovorin

Trattamento di controllo: 

Pembrolizumab + Chemotherapy

Centri partecipanti

Nord Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2024-514273-22-00 - NCT06780111

Data di inserimento: 16.12.2025

Promotore

Merck Sharp & Dohme LLC

Principal Investigator ITALIA

Riferimento: Dr. - -

Telefono: 00000

Email: na@na.it

Localita: -