INTerpath-013: A phase 2, randomized, double-blind study of intismeran autogene plus pembrolizumab and chemotherapy as first-line treatment for metastatic squamous non–small cell lung cancer.

Abstract

TPS8670 Background: Non–small-cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. The anti-PD-1 pembrolizumab plus platinum-based chemotherapy is a recommended treatment for metastatic squamous NSCLC. Despite the inclusion of anti-PD-(L)1 therapies into treatment guidelines, there remains an unmet medical need for further improving patient outcomes. Intismeran autogene (intismeran; formerly V940, mRNA-4157) is an investigational mRNA-based individualized neoantigen therapy (INT) encoding up to 34 neoantigens unique to each patient’s tumor and is designed to promote antitumor immune response. INTerpath-013 is a phase 2 study evaluating the addition of intismeran to pembrolizumab plus chemotherapy for previously untreated metastatic squamous NSCLC. Methods: This phase 2, randomized, double-blind, placebo-controlled study is enrolling patients aged ≥18 years with previously untreated histologically or cytologically confirmed stage IV squamous NSCLC (M1a, M1b, M1c1, or M1c2 per AJCC version 9) and measurable disease per RECIST v1.1 by investigator. Participants are also required to have ECOG PS 0 or 1 and provide a tumor sample for next-generation sequencing. Exclusion criteria include known active CNS metastases and/or carcinomatous meningitis, or untreated or symptomatic brain metastases. Approximately 180 participants will be randomized 2:1 to receive 1 treatment cycle comprising intravenous pembrolizumab 400 mg Q6W (1 dose) plus carboplatin AUC 6 mg/mL/min Q3W (2 doses), with either paclitaxel 200 mg/m 2 Q3W (2 doses) or nab-paclitaxel 100 mg/m 2 QW (6 doses). At week 6 (after cycle 1), tumor imaging will be performed and participants with complete response, partial response, or stable disease per RECIST v1.1 by BICR will continue 1 more treatment cycle and also receive up to 2 cycles of intismeran intramuscularly 1 mg (study arm A) or placebo (arm B) Q3W. All participants who complete the first 2 cycles of treatment will then receive up to 7 additional doses of intismeran or placebo (9 total) plus pembrolizumab up to 15 additional doses (17 total). Any participant with PD at the 6-week scan will have treatment unblinded and those in arm A may receive exploratory treatment with up to 9 doses of intismeran plus docetaxel 75 mg/m 2 Q3W until PD, unacceptable toxicity, or participant/physician decision; those in arm B will not receive further investigational treatment. Randomization will be stratified by PD-L1 tumor proportion score ( < 1% vs ≥1% to ≤49% vs ≥50%), ECOG PS (0 vs 1), and the number of metastatic sites (1 vs > 1). Primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints include ORR and duration of response per RECIST v1.1 by BICR and safety. Enrollment began in December 2025 and is ongoing across 55 global sites. Clinical trial information: NCT07221474 .