A Study to Evaluate Sacituzumab Tirumotecan (MK-2870) in Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-2870-015)

Phase 3

Recruiting

• Conditions: Gastroesophageal Cancer
• Interventions: Drug: Trifluridine-Tipiracil; Biological: Sacituzumab tirumotecan; Drug: Irinotecan; Drug: Rescue medication; Drug: Supportive care measures; Drug: Paclitaxel; Drug: Docetaxel

• Registration Number: NCT06356311
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This study will compare how safe and effective sacituzumab tirumotecan is versus the treatment of physician's choice (TPC) in participants with advanced/metastatic gastroesophageal adenocarcinoma. The primary hypothesis of this study is sacituzumab tirumotecan is superior to TPC with respect to Overall Survival (OS).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-04
• Study First Submitted QC: 2024-04-04
• Study First Posted: 2024-04-10
• Study Start: 2024-05-03
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-04
• Last Update Posted: 2025-07-08
• Primary Completion: 2027-01-04
• Study Completion: 2028-05-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• Has a histologically-or cytologically-confirmed diagnosis of advanced, unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma
• Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology. Lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions.
• Has received, and progressed on, at least 2 prior chemotherapy and/or immunotherapy regimens for advanced, unresectable or metastatic gastroesophageal adenocarcinoma.
• Participants are eligible regardless of human epidermal growth factor receptor-2 (HER2) status. Participants who are HER2+ must have previously received trastuzumab where available/appropriate
• Has adequate organ function
• Has provided tumor tissue sample for determination of trophoblast cell-surface antigen 2 (TROP2) status by the central laboratory before randomization for stratification
• Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine related AEs who are adequately treated with hormone replacement therapy are eligible
• Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days before randomization
• Has ability to swallow oral medication for those who may receive trifluridine-tipiracil
• Human immunodeficiency virus (HIV) infected participants must have well-controlled HIV on antiretroviral therapy (ART)
• Hepatitis B surface antigen (HBsAg) positive participants are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
• Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Exclusion Criteria

• Has a 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
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea)
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval (QTcF) to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention
• Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before the first dose of study intervention
• Has received prior treatment with a trophoblast antigen 2(TROP2) targeted antibody-drug conjugate (ADC), a topoisomerase 1 inhibitor based, and/or a topoisomerase 1 inhibitor-based chemotherapy.
• Has received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention
• Has received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has had radiation pneumonitis
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Is currently receiving a strong and/or moderate inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks
• Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active infection requiring systemic therapy
• HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castlemans's Disease
• Has concurrent active hepatitis B (defined as hepatitis B surface antigen (HBsAg) positive and/or detectable HBV deoxyribonucleic acid (DNA)) and Hepatitis C virus (HCV) defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection
• Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. Anticipation of the need for major surgery during the course of treatment with study intervention is also exclusionary
• Has severe hypersensitivity (Grades >=3) to the study interventions, any of their excipients, and/or to another biologic therapy
• Has a history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sacituzumab tirumotecan	Supportive care measures	Participants will receive sacituzumab tirumotecan at a dose of 4mg/kg by intravenous (IV) infusion on days 1, 15, and 29 of every 42-day cycle.
Treatment of Physician's Choice (TPC)	Trifluridine-Tipiracil	TPC include either trifluridine-tipiracil (35 mg/m\^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m\^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m\^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m\^2 IV on day 1 of every 21-day cycle).
Sacituzumab tirumotecan	Sacituzumab tirumotecan	Participants will receive sacituzumab tirumotecan at a dose of 4mg/kg by intravenous (IV) infusion on days 1, 15, and 29 of every 42-day cycle.
Treatment of Physician's Choice (TPC)	Docetaxel	TPC include either trifluridine-tipiracil (35 mg/m\^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m\^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m\^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m\^2 IV on day 1 of every 21-day cycle).
Treatment of Physician's Choice (TPC)	Supportive care measures	TPC include either trifluridine-tipiracil (35 mg/m\^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m\^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m\^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m\^2 IV on day 1 of every 21-day cycle).
Treatment of Physician's Choice (TPC)	Irinotecan	TPC include either trifluridine-tipiracil (35 mg/m\^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m\^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m\^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m\^2 IV on day 1 of every 21-day cycle).
Sacituzumab tirumotecan	Rescue medication	Participants will receive sacituzumab tirumotecan at a dose of 4mg/kg by intravenous (IV) infusion on days 1, 15, and 29 of every 42-day cycle.
Treatment of Physician's Choice (TPC)	Paclitaxel	TPC include either trifluridine-tipiracil (35 mg/m\^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m\^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m\^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m\^2 IV on day 1 of every 21-day cycle).

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to ~ 31 months	OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	Up to ~ 48 months	For participants who demonstrate a confirmed CR (disappearance of all target lesions) or 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.
Objective Response Rate (ORR)	Up to ~ 25 months	ORR is defined as the percentage of participants with CR (disappearance of all target lesions) or 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.
Number of Participants Who Discontinue Study Intervention Due to an AE	Up to ~ 48 months	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.
Progression-free survival (PFS)	Up to ~ 25 months	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 Response Criteria in Solid Tumors Version 1.1 (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 blinded independent central review (BICR) will be presented.
Number of Participants Who Experience an Adverse Event (AE)	Up to ~ 48 months	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.

Trial Locations

Locations (166)

Banner MD Anderson Cancer Center ( Site 0119); 🇺🇸 Gilbert, Arizona, United States

UCLA Hematology/Oncology - Santa Monica ( Site 0140); 🇺🇸 Los Angeles, California, United States

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0129); 🇺🇸 Orlando, Florida, United States

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0108); 🇺🇸 Marietta, Georgia, United States

University of Chicago Medical Center ( Site 0120); 🇺🇸 Chicago, Illinois, United States

University of Kentucky Chandler Medical Center-Medical Oncology ( Site 0124); 🇺🇸 Lexington, Kentucky, United States

The University of Louisville, James Graham Brown Cancer Center-James Graham Brown Cancer Center ( Site 0113); 🇺🇸 Louisville, Kentucky, United States

Norton Audubon Hospital-Norton Cancer Institute - Audubon ( Site 0105); 🇺🇸 Louisville, Kentucky, United States

Henry Ford Hospital ( Site 0107); 🇺🇸 Detroit, Michigan, United States

Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0138); 🇺🇸 Fargo, North Dakota, United States

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