Calculated Objective Response Rate (ORR) of 97% from Post-Hoc Analysis of a Phase 2 Multicenter Study to Evaluate the Efficacy of VP-315, an Investigational therapy for Basal Cell Carcinoma (BCC)

Introduction Objective response rate (ORR), defined as the percentage of patients achieving a complete or partial response to treatment, is a critical endpoint in clinical trials assessing the efficacy of new therapies in solid tumors, including BCC. We performed a post-hoc analysis exploring ORR as a potential primary endpoint for future studies evaluating the efficacy of VP-315, an intratumorally injected, chemotherapeutic oncolytic peptide. Objective To evaluate the effect of various VP-315 8 mg dosing regimens on antitumor response in subjects with BCC. Methods Eighty-two subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Post-hoc evaluation by ORR was based on response defined a priori as absence of disease progression and ≥30% reduction in lesion size from baseline, or complete resolution of ulceration in all target lesions. Complete response was based upon objective response with no residual BCC on post-treatment excisional biopsy. Partial response was objective response with presence of residual BCC. Results Eighty-two subjects (n=91 tumors) treated with VP-315 had a calculated ORR of 97%. Response rates were: 52% complete response and 45% partial response. No TRSAEs were reported. TRAEs were mostly mild to moderate. Conclusion These results support further investigation of ORR as a reliable endpoint for VP-315 in future BCC studies. Additional research using VP-315 as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting is warranted.