Phase 2 Study of BMS-986504 Monotherapy in Advanced/Metastatic NSCLC with Homozygous MTAP Deletion Post-Therapy Progression

The primary objective of this study is to evaluate the **objective response** (OR) by dose level in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with homozygous MTAP deletion. This is clinically relevant as it aims to determine the efficacy of BMS-986504 monotherapy in inducing a measurable response in tumor size or progression, which is crucial for assessing the potential benefit of the treatment in this patient population.

Secondary objectives include:

• Evaluating **disease control** (DC), **duration of response** (DOR), **progression-free survival** (PFS), and **time to objective response** (TTOR) by dose level, which are important for understanding the long-term benefits and stability of the treatment.
• Assessing safety and tolerability by dose level to ensure the treatment's risk profile is acceptable.
• Evaluating overall survival, which provides insight into the treatment's impact on extending life expectancy.
• Assessing the impact of disease symptoms and treatment on a participant’s health-related quality of life, which is vital for understanding the broader implications of the treatment on patient well-being.

The clinical trial involves a total of **56 participants** diagnosed with **Advanced or Metastatic Non-small Cell Lung Cancer**. The study population includes both male and female subjects, aged 18 years and older, who have a histologically confirmed diagnosis of NSCLC with a homozygous MTAP deletion detected in tumor tissue. Participants were selected based on their advanced or metastatic NSCLC status, which is not amenable to curative therapies after progression on prior treatments. All participants have at least one measurable lesion as per RECIST v1.1 and documented radiographic disease progression. The trial excludes vulnerable populations and requires participants to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Additionally, participants must be capable of swallowing. The selection criteria ensure that the study population is representative of individuals with advanced stages of the disease, providing a focused evaluation of the trial's main objective.

The clinical trial is a **randomized**, open-label, Phase 2 study designed to evaluate the safety and efficacy of BMS-986504 monotherapy in participants with advanced or metastatic **non-small cell lung cancer** (NSCLC) characterized by homozygous MTAP deletion. The primary objective is to assess the objective response (OR) by dose level, with secondary endpoints including disease control, duration of response, progression-free survival, and overall survival, all assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The trial is expected to commence recruitment on July 27, 2025, and conclude by December 30, 2031.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically confirmed diagnosis of NSCLC, documented radiographic disease progression, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The study will include follow-up visits to monitor treatment response and safety, with assessments conducted at regular intervals. The end-of-study visit will evaluate the overall outcomes and any long-term effects of the treatment.

The expected length of participant involvement will vary depending on individual response to treatment and disease progression, with the maximum treatment period set at 9999 days. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The investigational product, MRTX1719, will be administered orally in the form of a film-coated tablet, with the dosage tailored to the participant's response and tolerance.

The clinical trial involves the administration of the experimental medication **MRTX1719**, which is a **film-coated tablet**. The active substance in MRTX1719 is chemically synthesized and identified as **2-[4-[4-(aminomethyl)-1-oxo-2H-phthalazin-6-yl]-2-methylpyrazol-3-yl]-4-chloro-6-cyclopropyloxy-3-fluorobenzonitrile**. The medication is administered orally. The dosage and frequency of administration are determined based on the study protocol, with a maximum daily dose and total dose amount set at 9999 mg. The maximum treatment period is also specified as 9999 days, although specific dosing schedules are not detailed in the provided data. Participant compliance with the dosing regimen is monitored throughout the study.

In this study, MRTX1719 is used as a monotherapy for participants with advanced or metastatic **non-small cell lung cancer (NSCLC)** with homozygous MTAP deletion, following progression on prior therapies. There are no non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, mentioned in the trial data. The trial is designed to evaluate the objective response by dose level, and the pharmaceutical form of the medication is consistent with standard practices for oral administration. The study is conducted under the sponsorship of Bristol-Myers Squibb International Corporation, ensuring adherence to regulatory and ethical standards in clinical research.

The efficacy of the investigational product, MRTX1719, in the clinical trial will be assessed primarily through the **Objective Response (OR)** rate, utilizing the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. This primary endpoint will measure the number of participants who achieve an objective response, which includes complete or partial response as defined by RECIST criteria. Secondary endpoints will further evaluate efficacy through several parameters, including the number of participants achieving disease control (DC), duration of response (DOR), progression-free survival (PFS), and time to objective response (TTOR), all assessed by RECIST v1.1.

Additional secondary endpoints will include the number of participants experiencing adverse events (AEs) and serious adverse events (SAEs), as well as those with AEs leading to dose interruption, reduction, or discontinuation. Overall survival will also be monitored. Patient-reported outcomes will be assessed through changes from baseline in cancer-related symptoms and health-related quality of life, using the Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) and the EORTC-QLQ-F17 quality-of-life functional scale score. These assessments will provide a comprehensive evaluation of the treatment's impact on both clinical and patient-centered outcomes.