Phase 3 Study of Sacituzumab Govitecan vs. Physician's Choice in Endometrial Cancer Post-Platinum and Immunotherapy

The primary objective of this study is to compare **MK-2870** to Treatment of Physician's Choice (TPC) in terms of **progression-free survival** (PFS) and **overall survival** (OS) in participants with endometrial cancer who have previously received platinum-based chemotherapy and immunotherapy. Progression-free survival is a critical endpoint in oncology trials as it measures the length of time during and after treatment that a patient lives with the disease without it worsening. Overall survival is a definitive measure of treatment efficacy, reflecting the time from treatment initiation until death from any cause.

Secondary objectives include:

• Comparing MK-2870 to TPC with respect to the **objective response rate** (ORR) per RECIST 1.1 by blinded independent central review (BICR) in participants with measurable disease at baseline.
• Evaluating MK-2870 versus TPC concerning the **duration of response** (DOR) per RECIST 1.1 by BICR in participants with measurable disease at baseline.
• Assessing the **safety and tolerability** of MK-2870.
• Evaluating health-related **quality of life** (QoL) outcomes for MK-2870 versus TPC using the EORTC QLQ-C30.

The clinical trial involves a total of **443 participants** diagnosed with **endometrial cancer**. The study population is exclusively female, with an age range that includes adults and older adults. Participants were selected based on a histologically-confirmed diagnosis of endometrial carcinoma or carcinosarcoma, and they must have radiographically evaluable disease. Additionally, all participants have previously received platinum-based chemotherapy and anti-programmed cell death 1 protein (PD-1)/anti-programmed cell death ligand 1 (PD-L1) therapy. The trial does not include male subjects and involves a vulnerable population. Lifestyle factors such as diet, physical activity, or other habits are not specified in the available data.

The clinical trial is a **Phase 3**, randomized, active-controlled, open-label, multicenter study designed to evaluate the efficacy and safety of MK-2870 monotherapy compared to the treatment of physician's choice in participants with **endometrial cancer** who have previously received platinum-based chemotherapy and immunotherapy. The trial aims to assess progression-free survival (PFS) and overall survival (OS) as primary endpoints, with secondary endpoints including objective response rate (ORR), duration of response (DOR), and the incidence of adverse events (AEs). The study is expected to conclude by January 2028, with recruitment starting in December 2023.

Participants will be randomly assigned to receive either MK-2870 or a treatment regimen selected by their physician. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically-confirmed diagnosis of endometrial carcinoma or carcinosarcoma and prior treatment history. Follow-up visits will be scheduled to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.

The expected duration of participant involvement is up to 208 weeks, depending on individual response and tolerability. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial will be conducted in accordance with ethical guidelines and regulatory requirements, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **MK-2870**, a biological investigational product, formulated as a **powder for solution for injection**. The active substance is **sacituzumab tirumotecan**, a humanized IgG1 monoclonal antibody against TROP2, conjugated to KL610023. The maximum daily dose is 4 mg/kg, with a total maximum dose of 416 mg/kg over a treatment period of 208 weeks. The route of administration is **intravenous infusion**. Participant compliance will be monitored through regular assessments and adherence checks.

**Paclitaxel** is used as a comparator treatment in the study. It is a chemical-origin drug administered via **intravenous infusion**. The pharmaceutical form is coded as PHF00016MIG. The maximum daily dose is 80 mg/m², with a total maximum dose of 12,480 mg/m² over 208 weeks. Paclitaxel is known for its role in cancer treatment, particularly in chemotherapy regimens.

Another comparator treatment is **doxorubicin**, also of chemical origin, administered through **intravenous infusion**. The pharmaceutical form is PHF00231MIG. The maximum daily dose is 60 mg/m², with a total maximum dose of 450 mg/m² over a treatment period of 18 weeks. Doxorubicin is a well-established chemotherapeutic agent used in various cancer treatments.

**Acetylsalicylic acid** and **caffeine** are included as auxiliary treatments, with a pharmaceutical form coded as PHF00082MIG. These substances are administered both orally and intravenously, although specific dosing information is not provided. They are of chemical origin and are typically used for their analgesic and stimulant properties, respectively.

Additional auxiliary treatments include **glucocorticoids** and **antihistamines**, both of chemical origin. Glucocorticoids are administered through unspecified routes, while antihistamines are administered orally and intravenously. These treatments are included to manage potential side effects and support the primary treatment regimen.

The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include **Progression-Free Survival (PFS)** and **Overall Survival (OS)**, both evaluated per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR). Secondary endpoints encompass the Objective Response Rate (ORR) and Duration of Response (DOR), also per RECIST 1.1 as assessed by BICR. Additionally, the trial will monitor the number of participants experiencing one or more adverse events (AEs) and those who discontinue the study intervention due to an AE. Changes from baseline in Global Health Status/Quality of Life Score will be measured using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30).

The efficacy parameters will be collected and analyzed at various timepoints throughout the study, with assessments conducted by BICR to ensure objectivity and consistency. The trial is designed to compare the efficacy of MK-2870 monotherapy against the Treatment of Physician’s Choice in participants with endometrial cancer who have previously received platinum-based chemotherapy and immunotherapy. The study is structured as a Phase 3, randomized, active-controlled, open-label, multicenter trial, with an estimated end date of January 10, 2028.