Study of Combination Therapies in Esophageal Cancer

Phase 1/2

Active, not recruiting

• Conditions: Advanced esophageal squamous cell carcinoma (ESCC)

• Registration Number: 2023-505188-36-00
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

1. Safety Lead-in Phase: To evaluate the safety and tolerability of combination treatments that have not been evaluated in a separate study.

2. To estimate the objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-07-09
• Last Update Posted: 2025-06-25

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 20

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.

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.

History of allogenic tissue/solid organ transplant.

Clinically significant cardiovascular disease within 12 months from first dose of study intervention.

Participants with known gastrointestinal (GI) malabsorption or any other condition that may affect the absorption of lenvatinib.

Has risk for significant GI bleeding.

Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization.

Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization.

Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy.

Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase.		Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase.
Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase.		Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase.
Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase.		Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase.
Objective Response Rate (ORR).		Objective Response Rate (ORR).

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS).		Progression-Free Survival (PFS).
Duration of Response (DOR).		Duration of Response (DOR).
Overall Survival (OS).		Overall Survival (OS).
Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase.		Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase.
Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase.		Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase.

Trial Locations

Locations (11)

Fondazione IRCCS Istituto Nazionale Dei Tumori; 🇮🇹 Milan, Italy

Ospedale San Raffaele S.r.l.; 🇮🇹 Milan, Italy

Istituto Oncologico Veneto; 🇮🇹 Padova, Italy

Universitaetsklinikum Duesseldorf AöR; 🇩🇪 Duesseldorf, Germany

Krankenhaus Nordwest GmbH; 🇩🇪 Frankfurt Am Main, Germany

Charite Universitaetsmedizin Berlin KöR; 🇩🇪 Berlin, Germany

Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR; 🇩🇪 Dresden, Germany

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris, France

Centre Hospitalier Regional Et Universitaire De Brest; 🇫🇷 Brest, France

Centre Hospitalier Universitaire De Lille; 🇫🇷 Lille Cedex, France

Scroll for more (1 remaining)

Fondazione IRCCS Istituto Nazionale Dei Tumori

🇮🇹Milan, Italy

Filippo Pietrantonio

Site contact

00390223903807

filippo.pietrantonio@istitutotumori.mi.it