Phase 1 open-label study of ASP9801, an oncolytic virus, in patients with advanced or metastatic solid tumors.

[PURPOSE] ASP9801, an oncolytic virus encoding interleukin-7 and interleukin-12, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity in patients with advanced solid tumors in a Phase 1 study.

[METHODS] The study comprised Part 1 ASP9801 monotherapy dose escalation and Part 2 dose expansion with ASP9801 monotherapy or plus pembrolizumab. Each part was divided into Groups A (ASP9801 injection into cutaneous/subcutaneous lesions) and B (ASP9801 injection into visceral lesions). Primary objectives were safety and maximum tolerated dose and/or recommended Phase 2 dose expansion (RP2D); secondary objectives included antitumor activity and pharmacokinetics.

[RESULTS] In dose escalation, 17 and 10 patients in Groups A and B, respectively, received treatment. One dose-limiting toxicity (DLT; grade 3 cytokine release syndrome) was reported in Group A. Treatment-related adverse events (TRAEs) in ≥30% of patients in Group A were pyrexia and in Group B were pyrexia, chills, vomiting, nausea, fatigue, and headache. AEs leading to death occurred in two patients in Group A (one each for malignant neoplasm progression and sepsis); neither was attributed to ASP9801. The RP2D of ASP9801 was 5×10 plaque-forming unit/mL. In Part 2 dose expansion Group A, 12 patients received monotherapy RP2D, 5 received monotherapy induction, and 2 received ASP9801 plus pembrolizumab. In Group B, 9 and 11 patients received ASP9801 monotherapy or plus pembrolizumab, respectively. One DLT occurred in Group B combination safety cohort (grade 2 pyrexia and mental status change; grade 3 hypoxia, lymphopenia, and pneumonitis). During dose expansion, TRAEs in ≥30% of any cohort (>1 patient) in Group A were nausea, fatigue, chills, pyrexia, and headache and in Group B were nausea, vomiting, fatigue, chills, pyrexia, and lymphocyte count decreased. AEs led to death in two patients in Group A monotherapy and one patient in Group B monotherapy cohorts, all due to malignant neoplasm progression; none were attributed to ASP9801. One patient in Group B combination safety cohort achieved confirmed partial response (objective response rate, 9.1% (95% CI 0.3% to 52.7%)).

[CONCLUSIONS] Treatment with ASP9801 alone or plus pembrolizumab was generally well tolerated; however, the study was stopped due to lack of efficacy during dose expansion.