Phase 1/2a Open-Label Study of BMS-986507 in Combination with Pembrolizumab and Osimertinib Mesylate in Advanced Solid Tumors

The primary objective of this study is to evaluate the **safety** of BMS-986507 and determine the maximum safe dose for administration in combination with other treatments. This evaluation is crucial for identifying safe dosage levels that can be further assessed in a larger cohort of patients. The study focuses on two specific groups of lung cancer patients: those with EGFRmt non-small cell lung cancer (NSCLC) and those with EGFRwt NSCLC. Understanding the safety profile and optimal dosing of BMS-986507 in these populations is essential for advancing treatment options for patients with advanced solid tumors.

Secondary objectives include assessing how BMS-986507 behaves in the body when administered in combination with other treatments in Group A and Group B. This involves understanding the pharmacokinetics and the effects of BMS-986507 when used alongside other drugs, which is vital for optimizing therapeutic strategies and improving patient outcomes.

The clinical trial involves a total of **168 participants** diagnosed with **advanced solid tumors**, specifically focusing on two groups of lung cancer patients: those with EGFRmt non-small cell lung cancer (NSCLC) and those with EGFRwt NSCLC. The study population includes both male and female subjects, with an age range corresponding to adults and older adults. Participants were selected based on specific inclusion criteria, such as having at least one measurable lesion per response evaluation criteria in solid tumors, an Eastern Cooperative Oncology Group Performance Status of 0 or 1, and a life expectancy of at least three months at the time of the first dose. The trial does not include vulnerable populations. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The selection process ensures that participants are in a general health status that allows them to undergo the trial safely.

The clinical trial is designed as a **Phase 1/2a, open-label, dose-finding study** to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of BMS-986507 (BL-B01D1) in combination with other treatments in adult participants with advanced solid tumors. The trial will involve two groups of lung cancer patients: those with EGFRmt non-small cell lung cancer (NSCLC) and those with EGFRwt NSCLC. The study will assess the safety of BMS-986507 and determine the maximum safe dose for administration in combination with other treatments. The trial is expected to start recruitment on January 25, 2025, and conclude by August 15, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as having at least one measurable lesion per response evaluation criteria in solid tumors, an Eastern Cooperative Oncology Group Performance Status of 0 or 1, and a life expectancy of at least three months. Following the screening, participants will receive the investigational product and attend regular follow-up visits to monitor safety and efficacy outcomes. The primary endpoints include the number of participants with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs). Secondary endpoints will evaluate pharmacokinetic parameters such as maximum observed serum concentration (Cmax) and objective response rate (ORR).

The expected length of participant involvement will vary depending on individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include the occurrence of AEs leading to discontinuation or death, or if the participant no longer meets the inclusion criteria. The trial will utilize a combination of **intravenous** and **oral** administration routes for the investigational products, including pembrolizumab, osimertinib mesylate, and izalontamab brengitecan. The study aims to identify safe doses for further evaluation in a larger cohort of patients, contributing to the development of effective treatment regimens for advanced solid tumors.

**Pembrolizumab** is utilized in this clinical trial as a **concentrate for solution for injection**. It is administered via the **intravenous route**. The specific dosage and frequency of administration are determined based on the study protocol, which aims to evaluate its safety and efficacy in combination with other treatments. Pembrolizumab is a biological product of biotechnological origin, classified under the protein category. Participant compliance with the administration schedule is monitored throughout the trial to ensure adherence to the protocol.

**Osimertinib Mesylate** is provided in the form of a **film-coated tablet** and is administered **orally**. The dosage and frequency are specified in the study protocol, with the objective of assessing its safety and efficacy in combination with other investigational drugs. Osimertinib Mesylate is a chemical compound, and its administration is closely monitored to ensure participant compliance and accurate data collection.

**BL-B01D1**, also known as **Izalontamab Brengitecan**, is administered as a **powder for solution for infusion**. This investigational drug is delivered through the **intravenous route**. The study protocol outlines the dosing schedule, which is designed to evaluate the safety, tolerability, and preliminary efficacy of this biological product of biotechnological origin. Participant adherence to the dosing regimen is tracked to maintain the integrity of the trial data.

The clinical trial aims to assess the efficacy of **BMS-986507** (BL-B01D1) in combination with other treatments in adult participants with advanced solid tumors, specifically focusing on two groups of lung cancer patients: those with EGFRmt non-small cell lung cancer (NSCLC) and those with EGFRwt NSCLC. Efficacy will be evaluated using several secondary endpoints, including the objective response rate (ORR) and the duration of response (DOR). Pharmacokinetic parameters such as maximum observed serum concentration (Cmax), time of maximum observed concentration (Tmax), area under the concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)), and area under the serum concentration-time curve within a dosing interval (AUC(TAU)) will also be measured to provide additional insights into the drug's efficacy.

The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the trial. The trial is designed as a Phase 1/2a, open-label, dose-finding study, which will help determine the safety, tolerability, and preliminary efficacy of the treatment combinations. The trial is expected to conclude by August 15, 2028, with recruitment starting on January 25, 2025. The study will utilize validated methods to ensure the accuracy and reliability of the data collected, contributing to a comprehensive evaluation of the treatment's efficacy in the specified patient population.