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)

Launched by MERCK SHARP & DOHME LLC · Apr 1, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating new treatment options for patients with advanced esophageal squamous cell carcinoma, a type of cancer in the esophagus. It is focused on individuals who have already received at least one line of standard cancer treatment that included specific drugs known as PD-1/PD-L1 inhibitors but whose cancer has continued to progress. The study will evaluate the safety and effectiveness of these new agents, both alone and in combination with pembrolizumab (a type of immunotherapy) and/or chemotherapy.

To be eligible for this trial, participants should have confirmed advanced esophageal cancer, have experienced disease progression after prior treatment, and have a tumor sample available for analysis. They should also be in relatively good health, with manageable blood pressure and minimal side effects from previous treatments. Participants can expect to receive close monitoring throughout the study, and their responses to the new treatments will be carefully evaluated. This trial is currently recruiting patients aged 65 and older, and it aims to find better ways to help those dealing with this challenging cancer.

Gender

ALL

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)