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)
NCT Number: NCT06469944
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Gastroesophageal Junction|Gastroesophageal Adenocarcinoma|Esophageal Neoplasms|Esophageal Cancer
Interventions: BIOLOGICAL: Pembrolizumab|BIOLOGICAL: Sacituzumab Tirumotecan|DRUG: Capecitabine|DRUG: Leucovorin|DRUG: Levoleucovorin|DRUG: 5-FU
Sponsor: Merck Sharp & Dohme LLC
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 130
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-30
Completion Date: 2029-04-12
Locations: Cancer and Hematology Centers of Western Michigan ( Site 6912), Grand Rapids, Michigan, 49503, United States|Hematology-Oncology Associates of Central NY, P.C. ( Site 6925), East Syracuse, New York, 13057, United States|Hôpitaux Universitaires de Genève (HUG) ( Site 6701), Genève, Geneve, 1211, Switzerland

Summary:
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. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for sacituzumab tirumotecan in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.

Primary Outcome Measures: Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs), 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., Up to approximately 28 days|Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE), 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., Up to approximately 28 days|Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE, 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., Up to approximately 28 days|Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blind Independent Review Committee (BICR), 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., Up to approximately 28 months
Secondary Outcome Measures: Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR, PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. 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. PFS as assessed by BICR will be presented., Up to approximately 55 months|Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR, 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 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., Up to approximately 55 months|Overall Survival (OS), OS is defined as the time from randomization to the date of death from any cause., Up to approximately 55 months|Number of Participants Who Experience an Adverse Event (AE), 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., Up to approximately 55 months|Number of Participants Who Discontinue Study Treatment Due to an AE, 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., Up to approximately 55 months|Incidence of Antidrug Antibodies (ADA) to sacituzumab tirumotecan (sac-TMT, MK-2870), Blood samples collected at designated timepoints will be used to determine the ADA response to sac-TMT. The incidence of ADAs over time will be presented., Predose on Cycle 1 Days 1, 15, and 29; Cycle 2 Days 1, 15, and 29; Cycle 3 Days 1 and 15; Cycle 4 Days 1 and 29; and Cycle 5 Day 15 (each cycle length = 6 weeks)