Abstract 684P
Background
Neoantigen cancer vaccine (NCV) is a promising immunotherapy modality that aims to stimulate anti-tumor immune responses and synergize with immune checkpoint inhibitors to exert anti-tumor effects. This phase I trial intends to investigate the safety and tolerability of JCXH-212, a universal cancer vaccine targeting shared tumor neoantigens based on self-replicating RNA (srRNA) technology, alone or in combination with Toripalimab, an anti-PD1 monoclonal antibody, in patients with advanced NSCLC.
Methods
Patients with advanced NSCLC who progressed after standard treatments were enrolled. Part 1 comprised of a dose-escalation cohort of JCXH-212 with 2 dose levels of 100 μg and 200 μg administered intramuscularly once every 3 weeks. In Part 2, 2 dose level cohorts (100 μg and 200 μg) of JCXH-212 every 6 weeks combined with toripalimab 240 mg every 3 weeks were conducted. Primary objectives were to determine the MTD and the DLT of JCXH-212 with or without toripalimab. Peripheral blood mononuclear cells (PBMC) were collected to evaluate the antigen-specific T cell response via IFN-γ ELISPOT upon ex vivo restimulation with vaccine antigen peptide pools.
Results
9 patients with at least one matched neoantigens were enrolled. Median previous treatment lines were 4.5. The mean duration of JCXH-212 exposure was 31.7 days. No DLTs occurred during the study. 55.6% (5/9) patients experienced treatment-related adverse events (TRAE), most of which was pyrexia (55.6%), followed by injection site induration (11.1%). Most TRAEs were mild. No TRAEs lead to JCXH-212 dosage reduction, suspension, termination or death. There was 1 patient responding to JCXH-212 with a 2.1% decrease in the target lesion and 1 patient with stable disease up to 12 weeks. Analysis of PBMC revealed that JCXH-212 induced neoantigen-specific, IFN-γ producing T cell responses that could be further enhanced with toripalimab co-treatment.
Conclusions
JCXH-212 monotherapy or in combination with toripalimab demonstrated a tolerable safety profile and induced neoantigen-specific T cell immune responses in patients with advanced NSCLC. Further investigation of JCXH-212 in combination with toripalimab may be conducted in NSCLC.
Clinical trial identification
NCT05579275.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Immorna (Hangzhou) Biotechnology Co., Ltd.
Disclosure
Y. Liu, X. Guo, Z. Wang, N.T. Le, J. Fu, Y. Lin, F. Huang, M. Wang, H. Wu, Z. Guo: Financial Interests, Personal, Full or part-time Employment: Immorna (Hangzhou) Biotechnology Co., Ltd. All other authors have declared no conflicts of interest.