Phase II Randomized Trial of BMS-986012 with Carboplatin, Etoposide, and Nivolumab in First-line Treatment of Extensive-stage Small Cell Lung Cancer

The primary objective of this clinical trial is to assess the **safety** and **tolerability** of BMS-986012 in combination with carboplatin, etoposide, and nivolumab for participants with extensive-stage small cell lung cancer. This evaluation is crucial as it determines the feasibility of using this combination as a first-line therapy, comparing the induction and maintenance therapies of Arm A (BMS-986012 with nivolumab) versus Arm B (nivolumab alone).

Secondary objectives include:

• Estimating the progression-free survival rate (PFSR) at 6 and 12 months in each treatment arm, based on progression-free survival (PFS) by RECIST v1.1 as assessed by both blinded independent central review (BICR) and investigator.
• Comparing PFS as assessed by the investigator for participants treated in the combination induction and maintenance therapies of Arms A and B.
• Estimating the objective response rate (ORR), time to response (TTR), and duration of response (DOR) by RECIST v1.1 criteria, assessed by both BICR and investigator.
• Assessing overall survival (OS) of Arm A and Arm B and estimating the overall survival rate (OSR) at 12 and 24 months by treatment arm.
• Characterizing the immunogenicity of BMS-986012 in combination with carboplatin, etoposide, and nivolumab in Arm A.

The clinical trial involves a total of **50 participants** diagnosed with **extensive-stage small cell lung cancer**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically includes adults and older adults. Participants were selected based on specific criteria, including an Eastern Cooperative Oncology Group performance status of 0 or 1, the presence of at least one measurable lesion as determined by CT or MRI, and adequate hematologic and end organ function. The trial also considers lifestyle factors such as the agreement to follow specific methods of contraception, if applicable. The population includes vulnerable groups, ensuring a comprehensive assessment of the safety and tolerability of the treatment regimens under investigation.

The clinical trial is designed as a **randomized**, open-label, Phase II study to evaluate the safety and tolerability of BMS-986012 in combination with **carboplatin**, **etoposide**, and **nivolumab** as a first-line therapy for patients with extensive-stage small cell lung cancer. The trial involves two arms: Arm A, where participants receive BMS-986012 in combination with carboplatin, etoposide, and nivolumab for four cycles (induction) followed by BMS-986012 and nivolumab maintenance; and Arm B, where participants receive carboplatin, etoposide, and nivolumab for four cycles (induction) followed by nivolumab maintenance. The primary endpoints include the incidence of adverse events, serious adverse events, and progression-free survival as assessed by blinded independent central review based on RECIST v1.1 criteria. Secondary endpoints include progression-free survival rate, objective response rate, and overall survival.

The trial is expected to run from June 1, 2021, to December 15, 2026, with recruitment having started on March 17, 2021. Participants will be involved in the study for the duration of the treatment cycles and follow-up periods, with the possibility of early termination due to adverse events, lack of efficacy, or withdrawal of consent. The study visits include an initial screening visit to assess eligibility based on criteria such as ECOG performance status and measurable lesions, followed by regular visits during the treatment cycles to monitor safety and efficacy. The end-of-study visit will occur after the completion of the treatment and follow-up periods to assess the final outcomes and any long-term effects.

The clinical trial involves the administration of several experimental and non-experimental treatments. **Carboplatin** is utilized as a **solution for infusion**. It is a chemical compound with the active substance name carboplatin. The dosage form is a solution for infusion, and it is administered intravenously. The maximum daily and total dose amounts are set at 9999 mg/mL, with a treatment period extending up to 9999 days. The packaging and labeling of carboplatin have been modified for the trial.

The **Anti-Fucosyl GM1 PET Tracer**, with the active substance **[89ZR]BMS-986279**, is provided as a **solution for injection**. This protein-based tracer is administered intravenously. The dosage is measured in megabecquerels (MBq), with a maximum daily and total dose of 9999 MBq. The tracer is used to assist in the imaging and evaluation of the treatment's efficacy.

**OPDIVO**, containing the active substance **nivolumab**, is a **concentrate for solution for infusion**. It is a protein-based therapeutic agent administered via infusion. The dosage is expressed in milligrams, with a maximum daily and total dose of 9999 mg. OPDIVO is used in both the induction and maintenance phases of the trial.

The **Human IgG1 Monoclonal Antibody Against Fucosyl-GM1**, identified by the sponsor product code **BMS986012**, is provided as a **solution for injection**. This protein-based monoclonal antibody is administered intravenously. The dosage is measured in milligrams, with a maximum daily and total dose of 9999 mg. It is used in combination with other agents during the induction phase and as a maintenance therapy.

**Etoposide** is administered as a **solution for infusion**. It is a chemical compound with the active substance name etoposide. The dosage form is a solution for infusion, and it is administered intravenously. The maximum daily and total dose amounts are set at 9999 mg/mL, with a treatment period extending up to 9999 days. The labeling and packaging of etoposide have been modified for the trial.

The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary efficacy endpoint is **progression-free survival (PFS)**, which will be evaluated by blinded independent central review (BICR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Secondary endpoints include the progression-free survival rate (PFSR) at 6 and 12 months, objective response rate (ORR), time to response (TTR), duration of response (DOR), overall survival (OS), and overall survival rate (OSR). Additionally, the immunogenicity of BMS-986012 will be measured by assessing the presence of specific anti-drug antibodies (ADAs) to BMS-986012.

The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial. The PFS and other response-related endpoints will be assessed using imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) in accordance with RECIST v1.1 criteria. The trial will compare the efficacy of BMS-986012 in combination with carboplatin, etoposide, and nivolumab against a regimen of carboplatin, etoposide, and nivolumab alone, with maintenance therapy involving BMS-986012 and nivolumab or nivolumab alone. The trial is designed to provide a comprehensive evaluation of the treatment's efficacy in patients with extensive-stage small cell lung cancer.