A Phase II, Multicenter, Randomized, Double-Blind Study of Tobemstomig/RO7247669 Combined with Nab-Paclitaxel Compared with Pembrolizumab Combined with Nab-Paclitaxel in Participants with Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer

The primary objective of this study is to evaluate the **efficacy** of tobemstomig combined with nab-paclitaxel compared to pembrolizumab combined with nab-paclitaxel in the full analysis set (FAS) based on **progression-free survival** (PFS) in patients with previously untreated, PD-L1-positive, locally-advanced unresectable or metastatic **triple-negative breast cancer** (TNBC). This is clinically relevant as PFS is a critical endpoint in assessing the effectiveness of cancer therapies, providing insights into the duration a patient lives without disease progression.

Secondary objectives include:

• Evaluating the efficacy of tobemstomig plus nab-paclitaxel compared with pembrolizumab plus nab-paclitaxel in the FAS based on objective response rate (ORR), duration of response (DOR), and overall survival (OS).
• Assessing the safety of tobemstomig plus nab-paclitaxel compared with pembrolizumab plus nab-paclitaxel in the safety analysis set (SAS).

The clinical trial involves a total of **89 participants** diagnosed with **Triple-Negative Breast Cancer (TNBC)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including having metastatic or locally advanced unresectable TNBC, measurable disease per RECIST v1.1, and no prior systemic therapy for metastatic or locally advanced unresectable TNBC. Additionally, participants must have a tumor with programmed death-ligand 1 (PD-L1) expression and an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. The trial also requires adequate hematologic and end-organ function as defined by protocol-specified laboratory test results. The study population includes a vulnerable population, and lifestyle factors such as diet, physical activity, and habits were not specified by the sponsor.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of tobemstomig combined with nab-paclitaxel compared to pembrolizumab combined with nab-paclitaxel in participants with previously untreated, PD-L1-positive, locally-advanced unresectable or metastatic **triple-negative breast cancer** (TNBC). The primary endpoint is progression-free survival, with secondary endpoints including objective response rate, duration of response, overall survival, and the incidence and severity of adverse events. The trial is expected to conclude by October 2025, with recruitment having commenced in August 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically documented TNBC, measurable disease per RECIST v1.1, and adequate hematologic and end-organ function. Following the screening, participants will be randomized to receive either the investigational or comparator treatment. Regular follow-up visits will be scheduled to monitor treatment response and safety, with assessments including clinical laboratory tests and vital signs. The end-of-study visit will occur upon completion of the treatment period or in the event of disease progression or unacceptable toxicity.

The expected length of participant involvement is determined by the duration of treatment and follow-up, which may vary depending on individual response and tolerance to the therapy. Conditions that may lead to early termination from the study include withdrawal of consent, protocol non-compliance, or adverse events that compromise participant safety. The trial is conducted in accordance with ethical standards and regulatory requirements, ensuring the integrity and scientific validity of the research.

The clinical trial involves the administration of **Pembrolizumab**, also known by its synonyms Lambrolizumab, MK-3475, SCH-900475, and ABP 234. This experimental medication is marketed under the name **Keytruda** by MERCK SHARP & DOHME BV. It is a protein-based therapeutic agent, specifically categorized under "Protein - Other." The pharmaceutical form, dosage, route, and frequency of administration are not specified in the provided data. The medication has been re-labeled for clinical trial use, indicating its adaptation for investigational purposes within this study.

Another experimental treatment in the trial is **Tobemstomig**, identified by the sponsor product code RO 724-7669/F01-01 and produced by F. HOFFMANN-LA ROCHE LTD. This substance is also a protein-based agent, classified under "Protein - Other." The specific details regarding its pharmaceutical form, dosage, route, and frequency of administration are not detailed in the available information. Tobemstomig serves as a test product in the trial, aiming to evaluate its efficacy in combination with other treatments.

The trial also includes the administration of **Nab-Paclitaxel**, marketed as **Abraxane** by BRISTOL-MYERS SQUIBB PHARMA EEIG. This medication is categorized under "Specified Substance Group 1" and is a small molecule therapeutic agent. It has been re-labeled for clinical trial use, similar to Pembrolizumab. The pharmaceutical form, dosage, route, and frequency of administration are not provided in the data. Nab-Paclitaxel is used as a comparator treatment in the study, combined with both experimental medications to assess their relative efficacy.

Participant compliance with the dosing schedules and administration protocols will be monitored throughout the trial, although specific methods for compliance monitoring are not detailed in the provided information. The study aims to evaluate the efficacy of Tobemstomig plus Nab-Paclitaxel compared with Pembrolizumab plus Nab-Paclitaxel in participants with previously untreated, PD-L1-positive, locally-advanced unresectable or metastatic triple-negative breast cancer, focusing on progression-free survival as the primary outcome measure.

The efficacy of the clinical trial will be assessed primarily through **progression-free survival (PFS)** in the full analysis set (FAS). This endpoint will evaluate the time from randomization to the first documented disease progression or death from any cause, whichever occurs first. Secondary efficacy endpoints include the **objective response rate (ORR)**, **duration of response (DOR)**, and **overall survival (OS)**. Additionally, the incidence and severity of adverse events will be monitored, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0). Changes from baseline in targeted clinical laboratory test results and vital signs will also be evaluated.

The trial involves a comparison between two treatment regimens: Tobemstomig combined with nab-paclitaxel and Pembrolizumab combined with nab-paclitaxel, in participants with previously untreated, PD-L1-positive, locally-advanced unresectable or metastatic triple-negative breast cancer. Efficacy assessments will be conducted at specified intervals throughout the study duration, with data collection and analysis adhering to the predefined protocol. The study is designed to ensure rigorous evaluation of the treatment effects, contributing to the understanding of therapeutic benefits in this patient population.