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, and HER3-DXD plus ramucirumab 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.
Has histologically and/or cytologically confirmed diagnosis of previously treated, second line (2L) (received first line (1L) treatment) gastric adenocarcinoma, gastroesophageal junction 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
Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
Has squamous cell or undifferentiated gastroesophageal cancer
Has experienced weight loss >20% over 3 months before the first dose of study intervention
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 Grade ≥2 peripheral neuropathy
Parallel
Ramucirumab
Biological/Vaccine8 mg/kg IV Infusion
Paclitaxel
Drug80 mg/M\^2 IV infusion
Sacituzumab Tirumotecan
Biological/Vaccine3 mg/kg or 4 mg/kg IV Infusion
Rescue Medications
DrugParticipants 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.
HER3-DXd
Biological/VaccineIV Infusion
Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase
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
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
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)
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.
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Duration of Response (DOR)
For participants who demonstrate a confirmed 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 RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death from any cause. OS will be presented.
Percentage of Particiapants who Experience an AE During the Efficacy Phase
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.
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Merck Sharp & Dohme LLC
Lead sponsor
Daiichi Sankyo
Collaborator
