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)

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.

the master protocol is mk-3475-u06. as of protocol amendment 5, the pembrolizumab plus mk-4830 plus paclitaxel/irinotecan arm and the pembrolizumab plus mk-4830 plus lenvatinib arm are no longer actively enrolling participants.

Eligibility criteria:
the main inclusion and exclusion criteria include but are not limited to the following: inclusion criteria: * 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 therapy * has an evaluable baseline tumor sample (newly obtained or archival) for analysis * has adequately controlled blood pressure (bp) with or without antihypertensive medications * 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 criteria: * 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 corneal disease that prevents/delays corneal healing * has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease * 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 * 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 medication * 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 * active autoimmune disease that has required systemic treatment in past 2 years * participants with human immunodeficiency virus (hiv) with a history of kaposi's sarcoma and/or multicentric castleman's disease * concurrent active hepatitis b and hepatitis c virus infection * history of allogenic tissue/solid organ transplant * clinically significant cardiovascular disease within 12 months from first dose of study intervention * known gastrointestinal (gi) malabsorption or any other condition that may affect the absorption of lenvatinib. (not applicable to actively enrolling arms as of amendment 5) * has risk for significant 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. (not applicable to actively enrolling arms as of amendment 5)

Keywords: esophageal cancer programmed cell death 1 (pd1, pd-1) programmed cell death 1 ligand 1 (pdl-1, pd-l1) programmed cell death 1 ligand 2 (pdl-2, pd-l2)