A Phase 3 Study of MK-2870 Versus Investigator’s Choice of Non-platinum Chemotherapy in Participants with Pretreated Locally Advanced or Metastatic Urothelial Carcinoma

The primary objective of this study is to compare the overall survival of patients receiving sacituzumab tirumotecan versus an investigator’s choice of non-platinum chemotherapy in the treatment of pretreated locally advanced or metastatic urothelial carcinoma. Secondary objectives include the assessment of:

• Progression-free survival as measured by RECIST 1.1;
• Objective response rate per RECIST 1.1;
• Duration of response;
• Safety and tolerability;
• Changes from baseline in health-related quality of life and disease-related symptoms using the EORTC QLQ-C30.

This clinical trial involves 274 participants diagnosed with locally advanced or metastatic urothelial carcinoma. The study population includes both male and female patients within specific age ranges. To be eligible, participants must have measurable disease according to RECIST 1.1 and have received a maximum of three prior lines of therapy, including platinum-based chemotherapy, anti-PD-[L]1 therapy, and enfortumab vedotin. Additionally, patients must demonstrate an ECOG performance status of 0 or 1 and possess adequate organ function. Specific requirements are in place for individuals with viral infections, such as well-controlled HIV or undetectable HBV and HCV viral loads. The study aims to compare the efficacy of sacituzumab tirumotecan against investigator’s choice nonplatinum chemotherapy in terms of overall survival.

This Phase 3, randomized, open-label study is designed to compare the efficacy and safety of sacituzumab tirumotecan against an investigator’s choice of non-platinum chemotherapy in participants with locally advanced or metastatic urothelial carcinoma. The primary endpoint is overall survival. The comparator arms may include docetaxel, paclitaxel, or vinflunine administered via intravenous infusion. Secondary endpoints include progression-free survival, objective response rate, duration of response, and various assessments of quality of life and adverse events. The study involves a screening process to evaluate eligibility based on histologically documented disease, organ function, and prior treatment history, including platinum-based chemotherapy and enfortumab vedotin. Participants must have a measurable disease as defined by RECIST 1.1 and an ECOG performance status of 0 or 1. The estimated recruitment period and study duration extend through 2030. Specific conditions for early termination or discontinuation are not detailed in the provided data.

The experimental treatment consists of sacituzumab tirumotecan (MK-2870) provided as a solution for injection. This agent is administered via intravenous infusion at a dosage of 4 mg/kg.

Comparator treatments include docetaxel administered as an intravenous infusion at a dose of 75 mg/m2. Other comparator options consist of paclitaxel via intravenous infusion at 175 mg/m2 or vinflunine via intravenous infusion at 320 mg/m2.

The primary efficacy endpoint for this study is overall survival. Secondary efficacy endpoints include progression-free survival, objective response rate, and duration of response.

Efficacy is further evaluated through changes from baseline in several patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. These assessments include combined scores for global health status/quality of life, physical functioning, role functioning, fatigue, nausea/vomiting, and diarrhea.