EVM16（一种个性化mRNA新抗原疫苗）作为单药及与替雷利珠单抗联合治疗晚期实体瘤的首次人体（FIH）研究

Background: EVM16 Injection is a novel personalized mRNA cancer vaccine developed by Everest Medicines. Preclinical studies have demonstrated its potent neoantigen specific T-cell activation and significant tumor growth inhibition, together with a favorable safety and tolerability profile. As the FIH trial of EVM16, this study is conducted to evaluate safety, tolerability, and immunogenicity in patients with advanced solid tumors. Methods: This is a 3 + 3 dose-escalation study, consisting of three dose levels: 0.1 mg, 0.3 mg, and 1.0 mg. Patients with advanced or recurrent solid tumors who have failed standard of care and have at least one measurable target lesion will receive 2 doses of EVM16 monotherapy once every two weeks, followed by combination therapy of EVM16 (up to 7 doses, every 3 week [Q3W]) and Tislelizumab 200 mg (Q3W). After 9 doses of EVM16, 2 boost doses will be administered every 3 months when feasible. The primary endpoints are safety, tolerability, and the incidence of dose-limiting toxicity (DLT) observed within 28 days after the first administration. Other endpoints include immunogenicity and preliminary efficacy (objective response rate and progression-free survival [PFS]). Results: As of December 07, 2025, a total of 9 patients have been enrolled, each dose level consisting of 3 patients. All had completed the DLT assessment and undergone at least one efficacy evaluation. No DLT was observed. All patients experienced at least one investigational product (IP) related adverse event (AE), which were all Grade ≤ 2 and resolved spontaneously. The most frequent IP related AEs are injection site reactions (8/9, 88.89%), which all resolved without medical interventions. Other common IP related AEs are fever (7/9, 77.78%), fatigue (4/9, 44.4%), and anorexia (4/9, 44.4%), which all resolved spontaneously. EVM16 elicited strong neoantigen-specific T cell response in 8 out of the 9 patients, which showed a dose-dependent trend. A gastroesophageal junction cancer patient failed 3 prior lines of systemic therapy achieved a confirmed partial response and a PFS of 126 days. Another 2 patients achieved stable disease, including a non-small cell lung cancer patient failed 3 prior lines of systemic therapy achieved a PFS of 88 days, and an esophageal squamous cell carcinoma patient failed 3 prior lines of systemic therapy has been followed up for 112 days to date and has not experienced disease progression. Conclusion: EVM16 has demonstrated favorable safety and tolerability, robust immunogenicity, and promising efficacy signals, supporting further development. Subsequent studies are planned to explore the efficacy of EVM16 in early-stage treatment settings such as first-line and adjuvant therapies.