Overview
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.
Description
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
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 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-PD1/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.
- History of human immunodeficiency virus (HIV) infection.
- History of Hepatitis B or known active 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 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)