Recruiting

Phase 1

Phase 2

Investigational Agents & PembrolizumabA 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)

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT05319730

Conditions

Esophageal Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Paclitaxel

Irinotecan

Pembrolizumab

MK-4830

Lenvatinib

Study Details

Brief 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.

Conditions

Esophageal Squamous Cell Carcinoma

Study ID

NCT05319730

Start date

May 16, 2023

Status verified date

Sep, 2026

Completion date

Apr 10, 2029

Anticipated

Primary completion date

Jun 11, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 immune oncology (IO) therapy
Has provided an archival or most recent tumor tissue sample obtained as part of clinical practice
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 severe corneal disease that prevents/delays corneal healing
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
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
Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
History of allogenic tissue/solid organ transplant
Clinically significant cardiovascular disease within 12 months from first dose of study intervention
Has risk for significant gastrointestinal (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

Study Design

Enrollment

230 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Paclitaxel or irinotecan

Participants receive paclitaxel 80-100 mg/m\^2 intravenously (IV) on Days 1, 8, and 15 every 28-day cycle until progressive disease (PD) or discontinuation, or irinotecan 180 mg/m\^2 IV on day 1 of every 14-day cycle until PD or discontinuation.

experimental: Pembrolizumab + MK-4830 + paclitaxel or irinotecan

Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m\^2 IV on Days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m\^2 180 mg/m\^2 on day 1 every 14-day cycle until PD or discontinuation.

experimental: Pembrolizumab + MK-4830 + lenvatinib

Participants receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation.

experimental: Sacituzumab tirumotecan 4 mg/kg

Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

experimental: Sacituzumab tirumotecan 5 mg/kg

Participants will receive 5 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

Interventions

Paclitaxel

80-100 mg/m\^2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.

Irinotecan

180 mg/m\^2 IV infusion, administered on day 1 of every 14-day cycle.

Pembrolizumab

200 mg IV infusion, administered every Q3W up to 35 infusions.

MK-4830

800 mg IV infusion, administered Q3W up to 35 infusions.

Lenvatinib

20 mg oral administration every day.

Sacituzumab tirumotecan

4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.

Antihistamine