NCT06445972 · Merck Sharp & Dohme LLC
Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/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 effectiveness of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.
View original scientific description
This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.
Interventions
BIOLOGICAL
Ramucirumab
8 mg/kg IV Infusion
DRUG
Paclitaxel
80 mg/M\^2 IV infusion
BIOLOGICAL
Sacituzumab Tirumotecan
3 mg/kg or 4 mg/kg IV Infusion
DRUG
Rescue Medications
Participants receive rescue medications according to each approved drug's product label. Recommended rescue medications for the Sacituzumab Tirumotecan + Paclitaxel arm include antihistamines (histamine-1 and histamine-2 receptor antagonists), acetaminophen or equivalent, dexamethasone or equivalent infusion, and steroid mouth wash (dexamethasone or equivalent) and rescue medications for the HER3-DXd + ramucirumab arm include 5-HT3-receptor antagonist, NK-1 receptor antagonist, and corticosteroids.
BIOLOGICAL
HER3-DXd
IV Infusion
Primary outcome measures
Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase
Time frame: Up to ~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 presented.
Percentage of Particiapants who Experience an Adverse Event (AE) During the Safety Lead-In Phase
Time frame: Up to ~60 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. The percentage of participants who discontinued study intervention due to an AE will be presented.
Percentage of Participants who Discontinue Study Intervention Due to an AE During the Safety Lead-In Phase
Time frame: Up to ~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. The percentage of participants who discontinued study intervention due to an AE will be presented.
Objective Response Rate (ORR)
Time frame: Up to ~28 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.
Inclusion criteria
- The main inclusion criteria include but are not limited to the following:
- Has histologically and/or cytologically confirmed diagnosis of previously treated, 2L (received first line (1L) treatment) gastric adenocarcinoma, GEJ adenocarcinoma, or esophageal adenocarcinoma
- Has metastatic disease or locally advanced, unresectable disease
- Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy
- Participants with gastroesophageal adenocarcinoma that is known to be human epidermal growth factor receptor 2 (HER2)/neu positive are excluded. Participants with unknown HER2 status are eligible.
- Has provided an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion
- AEs due to previous anticancer therapies must be ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-relate
Where
- Tucson, Arizona
- Los Angeles, California
- Louisville, Kentucky
- Grand Rapids, Michigan
- East Syracuse, New York
- New York, New York
- Pittsburgh, Pennsylvania
- Houston, Texas
Collaborators
Daiichi Sankyo
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 Jul 6, 2026 · Source of record for eligibility and locations