1486 Preliminary results from LuCa-MERIT-1, a phase I trial evaluating BNT116, a fixed antigen mRNA vaccine, plus cemiplimab in advanced non-small cell lung cancer after progression on PD-1 inhibition

<h3>Background</h3> PD-1 inhibition is an effective first-line therapy for non-small cell lung cancer (NSCLC). After progression on first-line immunotherapy, one study found continued PD-1 inhibition or chemotherapy yielded limited benefits, with progression-free survival (PFS) of ~4.5 months and a disease control rate (DCR) of ~54.8% after chemotherapy.¹ BNT116 is an investigational therapeutic RNA-lipoplex cancer vaccine comprising six mRNAs each encoding a shared tumor-associated antigen. BNT116 showed a manageable safety profile and signs of efficacy with cemiplimab in heavily pre-treated NSCLC patients.² Here, we report preliminary results of BNT116+cemiplimab in patients with advanced PD-L1≥50% NSCLC progressing on or after anti-PD-(L)1. <h3>Methods</h3> LuCa-MERIT-1 (NCT05142189) is a first-in-human, open label, Phase I trial to determine safety and clinical activity of BNT116 alone or in combinations. Safety and clinical activity of BNT116+cemiplimab in NSCLC with PD-L1≥50% progressing after at least stable disease (SD) on PD-1 inhibitor-based first-line treatment is reported. Tumor and blood samples are used for biomarker analysis (immunogenicity, cytokines and circulating tumor DNA [ctDNA]). <h3>Results</h3> As of 01 SEP 2024, 20 patients (table 1) received BNT116+cemiplimab in the reported cohort (3+3 design). All patients experienced at least one treatment-emergent adverse event (TEAE), with 9/20 (45%) Grade 1/2, 11/20 (55%) Grade 3 and no Grade 4/5 TEAEs. Serious TEAEs were observed in 5/20 (25%) patients and included abdominal pain and adrenal insufficiency in one patient with adrenal gland metastases, general physical health deterioration and pleural effusion (one patient), confusional state (one patient), and pneumonitis (two patients). No dose limiting toxicities were observed. Two of 20 patients (10%) had a partial response (PR) and 14/20 patients (70%) had SD, resulting in an overall response rate of 10% and a DCR of 80%. Median duration of disease control was 6.2 months (95% CI: 4.0, NE), and median PFS was 5.5 months (95% CI: 2.9, 9.5). Robust cytokine induction was observed, and patients with progressive disease tended to have higher ctDNA levels at baseline and during early treatment compared with patients with SD/PR. Two patients tested with ELISpot showed responses to vaccine antigens, with pre-existing responses in one patient. <h3>Conclusions</h3> In this preliminary analysis, BNT116+cemiplimab had a manageable safety profile and showed encouraging DCR and PFS in patients previously progressing on PD-1 inhibition. Biomarker and updated safety and clinical activity data will be presented. In conclusion, the response profile suggests BNT116+cemiplimab may induce reversion of resistance to PD-1 inhibition in NSCLC. <h3>Acknowledgements</h3> LuCa-MERIT-1 is funded by BioNTech SE. The authors would like to acknowledge Anna Abad Sieper, Jana Foerster, Julia Setzer, Felicitas Tissen (BioNTech SE), Maximilian Tator and Kathrin John (BioNTech Diagnostics) for their contributions to the biomarker data and Florian Bock (BioNTech SE) for medical writing support. Cemiplimab was provided by Regeneron Pharmaceuticals, Inc. <h3>Trial Registration</h3> NCT05142189. <h3>References</h3> Metro Giulio, <i>et al.</i> ‘Outcomes from salvage chemotherapy or pembrolizumab beyond progression with or without local ablative therapies for advanced non-small cell lung cancers with PD-L1 ≥50% who progress on first-line immunotherapy: real-world data from a European cohort.’ <i>Journal of Thoracic Disease</i> 2019;<b>11</b>(12):4972–4981. doi:10.21037/jtd.2019.12.23. Deme Dániel, <i>et al.</i> ‘597 Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen RNA vaccine BNT116 in patients with advanced non-small cell lung cancer.’ <i>Journal for ImmunoTherapy of Cancer</i> 2023;<b>11</b>(Suppl 1):A679-A679. <h3>Ethics Approval</h3> This trial received relevant Ethics &amp; Institutional Review Board approvals in participating countries prior to initiation.