NCT05319730 · Merck Sharp & Dohme LLC
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)
What this study is about
This is a Phase 1/2, conducted at multiple hospitals, randomly assigned, where both patients and doctors know the treatment given umbrella platform study to evaluate the safety and effectiveness of experimental 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.
View original scientific description
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.
Interventions
DRUG
Paclitaxel
80-100 mg/m\^2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
DRUG
Irinotecan
180 mg/m\^2 IV infusion, administered on day 1 of every 14-day cycle.
BIOLOGICAL
Pembrolizumab
200 mg IV infusion, administered every Q3W up to 35 infusions.
BIOLOGICAL
MK-4830
800 mg IV infusion, administered Q3W up to 35 infusions.
DRUG
Lenvatinib
20 mg oral administration every day.
BIOLOGICAL
Sacituzumab tirumotecan
4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.
DRUG
Antihistamine
Administered per product label.
DRUG
H2 Receptor Antagonist
Administered per product label.
DRUG
Acetaminophen (or equivalent)
Administered per product label.
DRUG
Dexamethasone (or equivalent)
Administered per product label.
DRUG
Steroid Mouthwash (dexamethasone or equivalent)
Administered per product label.
DRUG
Supportive care measures
Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Artificial tear drops or ointment may be given as a supportive care for Ocular Surface Toxicity.
Primary outcome measures
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) During Safety Lead-in Phase
Time frame: Up to approximately 3 weeks
A DLT is defined as any drug-related AE according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle.
Number of Participants Who Experienced an Adverse Event (AE) During Safety Lead-in Phase
Time frame: Up to approximately 3 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase
Time frame: Up to approximately 3 weeks
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
Objective Response Rate (ORR)
Time frame: Up to approximately 48 months
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 aor
Where
- Tucson, Arizona
- Los Angeles, California
- East Syracuse, New York
- New York, New York
- Pittsburgh, Pennsylvania
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 26, 2026 · Source of record for eligibility and locations