Evaluation of Sacituzumab Tirumotecan With or Without Bevacizumab Versus Standard of Care in Platinum-Sensitive Recurrent Ovarian Cancer

The primary objective of this Phase 3, randomized, open-label, multicenter study is to evaluate the **safety** and tolerability of **sacituzumab tirumotecan** maintenance treatment with **bevacizumab** in participants with platinum-sensitive recurrent **ovarian cancer**. Additionally, the study aims to compare sacituzumab tirumotecan maintenance treatment, with or without bevacizumab, to the standard of care (SoC) with respect to progression-free survival (PFS) as assessed by blinded independent central review (BICR) using RECIST 1.1 criteria. This is clinically relevant as it may offer insights into more effective maintenance therapies for prolonging PFS in this patient population.

Secondary objectives include:

• Comparing sacituzumab tirumotecan maintenance treatment with or without bevacizumab to SoC in terms of overall survival (OS).
• Evaluating the safety and tolerability of sacituzumab tirumotecan maintenance treatment with or without bevacizumab.
• Assessing the mean change from baseline in global health status/quality of life (QoL) score using the EORTC QLQ-C30 and abdominal/gastrointestinal (GI) symptoms using the EORTC QLQ OV28 abdominal/GI symptom scale.

The clinical trial involves a total of **15 participants** who are exclusively female, as the study focuses on **recurrent ovarian cancer**. The age range of the participants spans from adults to the elderly, specifically categorized within the age groups of 18-64 and 65-84 years. Participants were selected based on specific inclusion criteria, including a histologically confirmed diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. They must have undergone multiple cycles of platinum-based chemotherapy and exhibit platinum-sensitive epithelial ovarian cancer. The trial does not include a vulnerable population, and participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial population was chosen to ensure a focus on the safety and tolerability of sacituzumab tirumotecan maintenance treatment with bevacizumab, as well as to compare its efficacy with standard care in terms of progression-free survival.

The clinical trial is a **Phase 3**, randomized, open-label, multicenter study designed to evaluate the efficacy and safety of **sacituzumab tirumotecan** maintenance treatment with or without **bevacizumab** compared to the standard of care in participants with platinum-sensitive recurrent ovarian cancer. The trial is structured into two parts: Part 1 focuses on assessing the safety and tolerability of sacituzumab tirumotecan with bevacizumab, while Part 2 compares the maintenance treatment with or without bevacizumab to the standard of care in terms of progression-free survival as per RECIST 1.1, assessed by blinded independent central review. The trial is expected to commence recruitment on February 26, 2025, and conclude by October 15, 2032, with a maximum treatment period of 84 days for participants.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed epithelial ovarian cancer, prior chemotherapy regimens, and performance status. Following randomization, participants will attend regular follow-up visits to monitor safety, adverse events, and treatment efficacy. The end-of-study visit will assess the overall outcomes and any long-term effects of the treatment. Participant involvement is anticipated to last for the duration of the treatment period, with conditions for early termination including the occurrence of adverse events or disease progression. The primary endpoints include the number of participants with adverse events and progression-free survival, while secondary endpoints focus on overall survival and quality of life assessments.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **Dexamethasone** is provided as an **oral solution** and is classified as a chemical substance. The specific dosage, route, and frequency of administration for dexamethasone are not detailed in the trial data. The maximum treatment period for dexamethasone is 84 days, and it is not a pediatric formulation.

**Bevacizumab** is administered as an **intravenous infusion**. It is a biological product with a maximum daily dose of 15 mg/kg and a total maximum dose of 1815 mg/kg over the treatment period. The treatment duration is set at 84 days. Bevacizumab is not formulated for pediatric use and is used in combination with other treatments in the trial.

**Sacituzumab tirumotecan**, also known by the sponsor product code **MK-2870**, is provided as a **powder for solution for injection**. This biological product is administered via intravenous infusion. The maximum daily dose is 4 mg/kg, with a total maximum dose of 728 mg/kg over the 84-day treatment period. Sacituzumab tirumotecan is not a pediatric formulation and is used as a test product in the trial.

Non-experimental treatments include a combination of **buclizine hydrochloride, paracetamol, and codeine phosphate**, which are chemical substances. The pharmaceutical form is not specified, and the route of administration is categorized as "other use." The maximum treatment period is 84 days, with no specified maximum daily or total dose. Additionally, **H2-receptor antagonists** and **antihistamines for systemic use** are included as auxiliary treatments, both classified as chemical substances with unspecified pharmaceutical forms and routes of administration. These treatments also have a maximum treatment period of 84 days, with no specified dosing information.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint for Part 2 of the trial is **Progression-free Survival (PFS)**, which will be evaluated according to RECIST 1.1 criteria as assessed by Blinded Independent Central Review (BICR). Secondary endpoints include Overall Survival (OS), the number of participants experiencing one or more adverse events (AEs), and the number of participants discontinuing the study intervention due to an AE. Additionally, changes from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status-Quality of Life Score, Physical Functioning Score, and Role Functioning Score will be measured. The EORTC Quality of Life Questionnaire-Ovarian Cancer Module 28 Abdominal/Gastrointestinal Symptom Scale will also be assessed.

Data collection for these endpoints will occur at specified intervals throughout the trial, with the schedule for assessments aligned with the trial's protocol. The use of validated scales and questionnaires, such as the EORTC QLQ-C30, ensures the reliability and accuracy of patient-reported outcomes. The trial is designed to compare the efficacy of sacituzumab tirumotecan maintenance treatment with or without bevacizumab against the standard of care in participants with platinum-sensitive recurrent ovarian cancer. The trial's estimated end date is October 15, 2032, with recruitment expected to start on February 26, 2025.