RecruitingPhase 1Phase 2NCT05319730

A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)

A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer Previously Exposed to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06B

Sponsor

Merck Sharp & Dohme LLC

Enrollment

230 participants

Start Date

May 16, 2023

Study Type

INTERVENTIONAL

Conditions

Esophageal Squamous Cell Carcinoma

Summary

This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable esophageal squamous cell carcinoma (ESCC)
Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy, that includes a platinum agent and previous exposure to an anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) based immune oncology (IO) therapy
Has provided an archival or most recent tumor tissue sample obtained as part of clinical practice
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 or participants who have ≤Grade 2 neuropathy are eligible

Exclusion Criteria11

Direct invasion into adjacent organs such as the aorta or trachea
Has experienced weight loss \>10% over approximately 2 months prior to first dose of study therapy
Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
History of allogenic tissue/solid organ transplant
Clinically significant cardiovascular disease within 12 months from first dose of study intervention
Has risk for significant gastrointestinal (GI) bleeding such as a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization, significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization

Interventions

DRUGPaclitaxel

80-100 mg/m\^2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.

DRUGIrinotecan

180 mg/m\^2 IV infusion, administered on day 1 of every 14-day cycle.

BIOLOGICALPembrolizumab

200 mg IV infusion, administered every Q3W up to 35 infusions.

BIOLOGICALMK-4830

800 mg IV infusion, administered Q3W up to 35 infusions.

DRUGLenvatinib

20 mg oral administration every day.

BIOLOGICALSacituzumab tirumotecan

4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.

DRUGAntihistamine