Final Results of a Phase II Multicenter Trial of HF10, a Replication-competent HSV-1 Oncolytic Virus, and Ipilimumab Combination Treatment in Stage IIIB-IV Unresectable or Metastatic Melanoma Patients
演題番号 : P123-8
1:Huntsman Cancer Institute, University of Utah, Salt Lake City, UT、2:The University of Texas MD Anderson Cancer Center, Houston, TX、3:St. Luke's Medical Center, Easton, PA and Temple university、4:Knight Cancer Institute, Oregon Health and Science University, Portland, OR、5:Penn State Hershey Cancer Institute, Hershey, PA、6:UC San Francisco, San Francisco, CA、7:Theradex Oncology, Princeton, NJ、8:Takara Bio. Inc, Shiga, Japan
HF10, a natural mutant strain of Herpes Simplex Virus type 1 (HSV-1), is a promising new oncolytic viral immunotherapy. Results of the Phase I trial (n=24) showed that HF10 is safe and well tolerated. Of 24 treated patients (pts), 7 pts had local and 8 pts had overall stable disease (SD); none had complete response (CR) or partial response (PR). Six of 9 melanoma pts who received no additional treatment (tx) after HF10 had delayed responses in HF10-injected lesions. The results showed the possible benefit of HF10 in tx of advanced metastatic melanoma. Herein, we report the safety and efficacy data of HF10 and ipilimumab (ipi) combination tx in a Phase II trial in melanoma.
Ipi naive pts with Stage IIIB-IV unresectable melanoma received HF10 inj. into single or multiple tumors (1X107 TCID50/ml/dose, up to 5ml depending on tumor size and number); 4 inj. qwk; up to 15 inj. q3w for 4 doses. Tumor responses assessed per irRC at 12, 18, 24, 36, 48wks. Primary endpoint was Best Overall Response Rate (BORR) at 24wks.
Of 46 pts enrolled and treated: 59% men, median age 67yrs (range 28-91); disease stage: 20% IIIB, 44% IIIC and 36% IV; tx naive: 57%; ≧1 prior cancer therapies: 43%. Most HF10-related AEs were ≦G2. 37% had≧G3 AEs, the majority due to ipi. Of 44 efficacy evaluable pts per irRC, BORR at 24wks was 41% (18% irCR, 23% irPR); disease stability rate was 68% (27% irSD). BORR at 24wks in tx naive pts was 50% (17% irCR, 33% irPR) and pts with ≧1 prior cancer therapies was 30% (20% irCR, 10% irPR). BORR at 48wks was 45% (18% irCR, 27% irPR). As of 19APR2017, median PFS was 19 months; 1-year overall survival rate was 85%.
The combination HF10 and ipi show favorable benefit/risk profile and encouraging antitumor activity in unresectable or metastatic melanoma pts.