NCT06469944 · Merck Sharp & Dohme LLC
Substudy 06C: A Study of Sacituzumab Tirumotecan (MK-2870) With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)
What this study is about
This is a phase 1/2, conducted at multiple hospitals, where both patients and doctors know the treatment given umbrella platform study that will evaluate the safety and how well patients handle the treatment of sacituzumab tirumotecan with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an effectiveness phase.
View original scientific description
This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of sacituzumab tirumotecan with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase.
Interventions
BIOLOGICAL
Pembrolizumab
Administered via intravenous (IV) infusion.
BIOLOGICAL
Sacituzumab Tirumotecan (sac-TMT)
Administered via IV infusion.
DRUG
Capecitabine
Administered via oral tablet.
DRUG
Leucovorin
Administered via IV infusion.
DRUG
Levoleucovorin
Administered via IV infusion.
DRUG
5-Fluorouracil (5-FU)
Administered via IV infusion
DRUG
Oxaliplatin
Administered via IV infusion
BIOLOGICAL
Patritumab Deruxtecan
Administered via IV infusion
Primary outcome measures
Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
Time frame: Up to approximately 28 days
DLTs are defined as any drug-related adverse event (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. The percentage of participants who experience at least one DLT will be reported.
Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 28 days
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE
Time frame: Up to approximately 28 days
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time frame: Up to approximately 28 months
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by 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.
Inclusion criteria
- The main inclusion criteria include but are not limited to the following:
- Has histologically and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic 1L gastroesophageal adenocarcinoma
- Has gastroesophageal adenocarcinoma that is known to be human epidermal growth factor receptor 2 (HER2)/neu-positive are excluded. HER2 status is not required if HER2/neu testing is not mandatory per local standard of care (SOC)
- Is not expected to require tumor resection during the treatment course
- Has not had prior systemic therapy administered in the recurrent or metastatic setting
- Has provided an archival tumor tissue sample or most recently obtained core, or incisional, or excisional biopsy for a tumor lesion
- 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 repl
Where
- Tucson, Arizona
- Los Angeles, California
- Louisville, Kentucky
- Grand Rapids, Michigan
- East Syracuse, New York
- New York, New York
- Pittsburgh, Pennsylvania
- Houston, Texas
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 May 26, 2026 · Source of record for eligibility and locations