Subgroup analysis of a phase II multicenter trial of HF10, oncolytic virus immunotherapy, and ipilimumab combination treatment in unresectable or metastatic melanoma patients

Abstract

Background: HF10 is a bioselected replication-competent oncolytic virus derived from HSV-1. Herein, we report the safety and efficacy data of HF10+ipilimumab (ipi) combination treatment in a Phase II trial in melanoma. Methods: Ipi naïve patients (pts) with Stage IIIB-IV unresectable melanoma received HF10 injections (inj) into single or multiple dermal, subcutaneous or lymph node tumors (1x107 TCID50/mL, up to 5mL/dose); 4 inj qwk; then up to 15 inj q3wk. Ipi was administered IV (3 mg/kg), q3wk for 4 doses. Tumor responses assessed per irRC at 12, 18, 24, 36 and 48wks. Primary endpoint was Best Overall Response Rate (BORR) at 24wks. Results: Of 46 pts enrolled and treated: 59% men, median age 67 yrs (range 28 to 91); disease stage 20% IIIB, 43% IIIC &37% IV; therapy (tx) naïve: 57% and 1 prior cancer tx: 43% (2 pts received prior immune checkpoint inhibitors). Most HF10-related AEs wereG2, similar to HF10 monotherapy. 37% had G3 AEs, the majority due to ipi. HF10-related G3 AEs (n 3) were embolism, lymphedema, diarrhea, hypoglycemia, and groin pain. Of 44 efficacy evaluable pts per irRC, BORR at 24wks was 41% (18% irCR, 23% irPR); disease control rate was 68% (27% irSD). BORR at 48wks was 45% (18% irCR, 27% irPR). BORR at 24wks in tx naïve pts was 50% (17% irCR, 33% irPR) and pts with 1 prior therapies was 30% (20% irCR, 10% irPR). BORR in pts with stages IIIB/IIIC/IVM1a (n 34) and IVM1b/IVM1c (n 10) were 47% (21% irCR, 26% irPR) and 20% (10% irCR, 10% irPR), respectively. Median PFS was 19mos and 1-year overall survival rate was 85%. Median PFS in tx naïve and pts with 1 prior therapies were 19mos and 22mos, respectively; 1-year overall survival rates in tx naïve and pts with 1 prior therapies 87% and 82%, respectively. HF10+ipi treatment resulted in a decrease in lesion size by 50% in 57% of injected lesions (N 148), 39% of never injected non-visceral lesions (N 41) and 14% of never injected visceral lesions (N 22). Complete resolution of lesions occurred in 30% of injected lesions and 20% of never injected non-visceral lesions. Conclusions: The combination HF10 and ipi treatment demonstrated a favorable benefit/risk profile and encouraging antitumor activity in unresectable or metastatic melanoma pts.