Phase II Randomized, Double-Blind Study of BMS-986315 and Nivolumab with Chemotherapy in Stage IV or Recurrent Non-Small Cell Lung Cancer

The primary objective of this study is to evaluate the **safety** of BMS-986315 when administered in combination with nivolumab and histology-based platinum doublet chemotherapy (PDCT) in participants with Stage IV or recurrent **non-small cell lung cancer** (NSCLC). Additionally, the study aims to compare the anti-tumor activity, specifically the objective response rate (ORR), of BMS-986315 and nivolumab in combination with PDCT versus nivolumab and PDCT alone. This is clinically relevant as it seeks to determine the efficacy and safety of a novel therapeutic combination in a first-line treatment setting for NSCLC, potentially offering improved outcomes for patients.

Secondary objectives include further assessment of preliminary anti-tumor activity, such as progression-free survival (PFS), and characterization of the pharmacokinetics (PK) and immunogenicity of BMS-986315. These objectives are crucial for understanding the drug's behavior in the body and its potential to provoke an immune response, which are important factors in the development of effective cancer therapies.

The clinical trial involves a total of **101 participants** diagnosed with **Non-small Cell Lung Cancer** (NSCLC). The study population includes both male and female subjects who are **18 years of age or older**. Participants are required to have Stage IV or recurrent NSCLC following multimodal therapy for locally advanced disease, and the study treatment must be their first-line therapy for Stage IV or recurrent disease. All participants must have measurable disease according to RECIST v1.1 criteria, an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, and a life expectancy of at least three months at the time of the first dose. The trial population was selected based on these criteria, ensuring that individuals have a consistent baseline for evaluating the safety and efficacy of the treatment regimen. The study does not specify any particular lifestyle considerations such as diet or physical activity. Both vulnerable and non-vulnerable populations are included in the trial, reflecting a diverse participant group.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy and safety of BMS-986315 and **nivolumab** in combination with chemotherapy compared to nivolumab with chemotherapy alone in patients with Stage IV or recurrent **non-small cell lung cancer** (NSCLC). The trial is structured in two parts: a safety lead-in phase and a primary efficacy phase. The trial is expected to commence recruitment on February 17, 2024, and conclude by March 30, 2027, with an estimated duration of 24 months for participant involvement.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, disease stage, and performance status. Following successful screening, participants will be randomized into treatment groups. The trial includes multiple follow-up visits to monitor safety, adverse events, and treatment efficacy, with assessments conducted according to RECIST v1.1 criteria. The primary endpoint is the objective response rate (ORR) evaluated by a blinded independent central review committee. Secondary endpoints include pharmacokinetic parameters and additional efficacy measures such as progression-free survival (PFS).

The end-of-study visit will occur after the completion of the treatment period or upon early termination. Conditions that may lead to early termination include significant adverse events, disease progression, or withdrawal of consent. Participants will receive treatment via **intravenous infusion**, with the investigational products administered according to the specified dosing regimen. The trial aims to provide comprehensive data on the safety and anti-tumor activity of the investigational combination therapy in the specified patient population.

The clinical trial involves the administration of several experimental and comparator medications. **Cisplatin** is utilized as a **concentrate for solution for infusion**. It is administered via **intravenous infusion** with a maximum daily dose of 75 mg/m² and a total dose not exceeding 300 mg/m² over a treatment period of up to 12 weeks. Cisplatin is a chemical substance used as a comparator in this study.

**Opdivo** (Nivolumab) is provided as a **10 mg/mL concentrate for solution for infusion**. This biological agent is administered through **intravenous infusion** with a maximum daily dose of 360 mg and a total dose of up to 11,520 mg over a 24-week period. Nivolumab serves as a test treatment in combination with other agents.

**Paclitaxel** is another **concentrate for solution for infusion** used in the trial. It is administered via **intravenous infusion** with a maximum daily dose of 200 mg/m² and a total dose not exceeding 800 mg/m² over a 12-week treatment period. Paclitaxel is a chemical substance used as a comparator.

The investigational drug **anti-NKG2A mAb** (BMS-986315) is provided as a **solution for injection**. It is administered through **intravenous infusion** with a maximum daily and total dose of 9999 mg over a 24-week period. This biological agent is the primary test treatment in the study.

**Pemetrexed Disodium** is supplied as a **powder for concentrate for solution for infusion**. It is administered via **intravenous infusion** with a maximum daily dose of 500 mg/m² and a total dose of up to 16,000 mg/m² over a 24-week period. Pemetrexed Disodium is a chemical substance used as a comparator.

**Carboplatin** is used as a **concentrate for solution for infusion**. It is administered through **intravenous infusion** with a maximum daily dose of 900 mg/m² and a total dose not exceeding 3600 mg/m² over a 12-week treatment period. Carboplatin is a chemical substance used as a comparator in this study.

Efficacy in this clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**, which will be evaluated by a Blinded Independent Central Review (BICR) committee. This endpoint is crucial for comparing the anti-tumor activity of the combination of BMS-986315 and nivolumab with platinum doublet chemotherapy (PDCT) versus nivolumab with PDCT alone in participants with Stage IV or recurrent Non-Small Cell Lung Cancer (NSCLC). The ORR will provide insights into the proportion of patients who experience a predefined level of tumor size reduction.

Secondary efficacy endpoints will include additional anti-tumor efficacy parameters such as Progression-Free Survival (PFS), also assessed by BICR. These measures will help to further understand the treatment's impact on delaying disease progression. The trial will also summarize pharmacokinetic (PK) parameters of BMS-986315 to evaluate its behavior in the body when administered in combination with nivolumab and chemotherapy.