Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal... | NCT04949256 | Trialant

Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal... | NCT04949256 | Trialant

Official Title: A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma.
Brief Summary: The purpose of this study is to assess the efficacy and safety of pembrolizumab plus lenvatinib plus chemotherapy compared with pembrolizumab plus chemotherapy as first-line intervention in participants with metastatic esophageal carcinoma.

The primary hypotheses are that pembrolizumab plus lenvatinib plus chemotherapy is superior to pembrolizumab plus chemotherapy with respect to overall survival (OS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

As of Amendment 09, Study MK-7902-014 will begin close out activities. Any participant who discontinues study intervention for any reason will be discontinued from the study without further follow-up. Second Course and treatment beyond disease progression will no longer be offered. No safety concerns contributed to the termination of this study.
Detailed Description: There will be 2 parts to the study: the cisplatin and 5-fluorouracil (5-FU) (FP) and paclitaxel and cisplatin (TP) Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (FP and TP Safety Run-in), participants will be treated with pembrolizumab plus lenvatinib plus FP or TP. Dose-limiting toxicities, safety, and tolerability will be assessed.

In Part 2 (Main Study), participants (not including those participating in Part 1) will be treated with pembrolizumab plus lenvatinib plus chemotherapy or pembrolizumab plus chemotherapy. Efficacy, safety, and tolerability will be assessed.

The protocol-specified analysis of the primary outcome measures was completed with a data cut-off of 08-May-2025 (Primary Completion Date) and served as the final analysis of the primary outcome measures. At the time of the protocol-specified analysis, 368 participants were ongoing in the study and will be included in the End of Trial analysis.

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Eligibility Criteria: Inclusion Criteria:

Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus

Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comes last; 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only and is greater than 90 days post chemotherapy, no male contraception is needed

Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 120 days after the last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last dose of chemotherapy, whichever occurs last, and agrees not to donate eggs during this period

Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week prior to randomization

Has adequate organ function

Exclusion Criteria:

Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer

Has locally advanced esophageal carcinoma

Has metastatic adenocarcinoma of the esophagus

Has direct invasion into adjacent organs such as the aorta or trachea

Has radiographic evidence of encasement of a major blood vessel, or of intratumoral cavitation

Has perforation risks or significant gastrointestinal (GI) bleeding

Has had clinically significant hemoptysis within 3 weeks prior to the first dose of study drug or tumor bleeding within 2 weeks prior to the first dose of study intervention

Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention

Has GI obstruction, poor oral intake, difficulty in taking oral medication, or existing esophageal stent

Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks prior to first dose of study interventions

Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis

Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed

Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention, or has a history of organ transplant, including allogeneic stem cell transplant

Has a 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 an active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed

Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease

Has poorly controlled diarrhea

Has clinically significant cardiovascular disease within 12 months from first dose of study intervention

Has peripheral neuropathy ≥Grade 2

Has a known history of human immunodeficiency virus (HIV) infection

Has a known history of Hepatitis B or know active Hepatitis C virus infection

Has a weight loss of >20% within the last 3 months