Phase 2 Study of V940 in Combination with Pembrolizumab and Combination Therapy for First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer

The primary objective of this study is to compare the efficacy of V940 in combination with pembrolizumab and platinum chemotherapy versus placebo in participants with metastatic squamous non-small cell lung cancer. Clinical relevance is established through the evaluation of progression-free survival, assessed by blinded independent central review using RECIST 1.1, and overall survival. Secondary objectives include the assessment of objective response rate and duration of response, alongside an evaluation of safety and tolerability.

This study involves 123 participants diagnosed with squamous non-small cell lung cancer at stage IV. The study population consists of both male and female individuals aged 18 years or older. Eligible participants must have measurable disease according to RECIST 1.1 and a life expectancy of at least 3 months. Required characteristics include adequate organ function and an ECOG performance status of 0 to 1. Participants must have provided a tissue sample from a site that has not been previously irradiated. Specific requirements are in place for those with human immunodeficiency virus, hepatitis B, or hepatitis C, necessitating well-controlled viral loads or completed antiviral therapy. Any adverse events from prior anticancer therapies must have recovered to a grade of 1 or less, with certain allowances for endocrine-related issues or neuropathy. The primary objectives of the trial are:

• To compare V940 versus placebo in combination with pembrolizumab and platinum chemotherapy regarding progression-free survival.
• To compare V940 versus placebo in combination with pembrolizumab and platinum chemotherapy regarding overall survival.

This is a Phase 2, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy of V940 in combination with pembrolizumab and platinum chemotherapy as a first-line treatment for individuals with metastatic squamous non-small cell lung cancer. The research methodology compares V940 against a placebo to assess primary endpoints, including progression-free survival and overall survival. Study products involve various intravenous infusion therapies, such as carboplatin, paclitaxel, or docetaxel, along with mRNA-4157 administered via intramuscular use. The trial is estimated to conclude by February 21, 2031. The study includes a screening phase to confirm histological diagnosis and measurable disease per RECIST 1.1 criteria, followed by the treatment period and subsequent monitoring to evaluate secondary endpoints such as objective response rate and duration of response. Early termination of study participation may occur due to adverse events or discontinuation of study therapy.

mRNA-4157 is administered as a dispersion for injection via intramuscular use at a dose of 1 mg.

Pembrolizumab is provided as a solution for infusion at a dose of 400 mg via intravenous infusion.

Carboplatin is administered via intravenous infusion at a dose of 900 mg.

Paclitaxel is administered via intravenous infusion at a dose of 200 mg/m².

Paclitaxel albumin-bound is administered via intravenous infusion at a dose of 100 mg/m².

Docetaxel is administered via intravenous infusion at a dose of 75 mg/m².

A placebo to V940 is utilized in the study design.

The efficacy of the study intervention in participants with metastatic squamous non-small cell lung cancer will be evaluated using several primary and secondary endpoints. The primary assessment of efficacy focuses on progression-free survival (PFS) and overall survival (OS).

Progression-free survival will be determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and will be evaluated by blinded independent central review (BICR). Secondary efficacy parameters include the objective response rate (ORR) and the duration of response (DOR).