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

Gastroesophageal Cancer Clinical Trial

Official title:

A Phase 3, Multicenter, Open-label, Randomized Study to Compare the Efficacy and Safety of MK-2870 Versus Treatment of Physician's Choice in 3L+ Advanced/Metastatic Gastroesophageal Adenocarcinoma (Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, and Esophageal Adenocarcinoma)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06356311
• Other study ID #: 2870-015
• Secondary ID: 2023-505423-31U1
• Status: Recruiting
• Phase: Phase 3
• Start date: May 3, 2024
• Est. completion date: May 5, 2028

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: May 5, 2028
• Est. primary completion date: January 4, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a histologically-or cytologically-confirmed diagnosis of advanced, unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma.
• Has received, and progressed on, at least 2 prior chemotherapy and/or immunotherapy regimens.
• Participants are eligible regardless of human epidermal growth factor receptor-2 (HER2) status. Participants who are HER2+ must have previously received trastuzumab.
• 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.

Exclusion Criteria:

• Has experienced weight loss >20% over 3 months before the first dose of study intervention.
• Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or 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 the study. The required washout period before starting sacituzumab tirumotecan 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 CNS metastases and/or carcinomatous meningitis.- Has an active infection requiring systemic therapy.
• Has a history of human immunodeficiency virus (HIV) infection.- Has concurrent active hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive and/or detectable hepatitis B virus (HBV) deoxyribonucleic acid (DNA)) and/or hepatitis C (defined as anti-hepatitis C virus (HCV) antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection or a known history of hepatitis B and/or C infection.
• Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention.
• Has severe hypersensitivity (Grades >=3) to sacituzumab tirumotecan, any of its excipients, and/or to another biologic therapy.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastroesophageal Cancer

Intervention

Biological:
• Sacituzumab tirumotecan
Participants will receive sacituzumab tirumotecan as 4mg/kg IV infusion on days 1, 15, and 29 of every 42-day cycle.

Drug:
• Trifluridine-Tipiracil
Trifluridine-tipiracil will be administered at 35 mg/m^2 as tablet orally twice a day on days 1-5 and 8-12 of every 28-day cycle.
• Irinotecan
Irinotecan will be administered at a dose of 150 mg/m^2 by IV infusion on days 1 and 15 of every 28-day cycle.
• Paclitaxel
Paclitaxel will be administered at a dose of 80 mg/m^2 by IV infusion on days 1, 8 and 15 of every 28-day cycle.
• Docetaxel
Docetaxel will be administered at a dose of 75 mg/m^2 by IV infusion on day 1 of a 21-day cycle.

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus-Oncology Division ( Site 1600)	Haifa
Taiwan	National Cheng Kung University Hospital-Clinical Trial Center ( Site 3604)	Tainan
United States	Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0108)	Marietta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Israel,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~ 31 months
Secondary	Progression-free survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression per response evaluation criteria in solid tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) or death due to any cause, whichever occurs first.	Up to ~ 25 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR.	Up to ~ 25 months
Secondary	Duration of Response (DOR)	DOR is defined as the time from the first documented evidence of confirmed CR or PR until the first documented date of disease progression or death due to any cause, whichever occurs first.	Up to ~ 48 months
Secondary	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 ~ 48 months
Secondary	Number of Participants Who Discontinue 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 ~ 48 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary