378O - Subgroup Analysis of a Phase II Multicenter Trial of HF10, Oncolytic Virus Immunotherapy, and Ipilimumab Combination Treatment in Unresectable or M...

Date 18 November 2017
Event ESMO Asia 2017 Congress
Session Proffered paper session 2
Topics Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Robert Andtbacka
Citation Annals of Oncology (2017) 28 (suppl_10): x113-x116. 10.1093/annonc/mdx667
Authors R.H.I. Andtbacka1, M. Ross2, S.S. Agarwala3, M. Taylor4, J. Vetto4, R.I. Neves5, A. Daud6, H.T. Khong1, R.S. Ungerleider7, M. Tanaka8, K.F. Grossmann1
  • 1-, Huntsman Cancer Institute, University of Utah, 84103 - Salt Lake City/US
  • 2-, The University of Texas, MD Anderson Cancer Center, Houston/US
  • 3-, St. Luke's University Hospital and Temple University, Easton/US
  • 4-, Knight Cancer Institute, Oregon Health and Science University, Portland/US
  • 5-, Penn State Hershey Cancer Institute, Hershey/US
  • 6-, University of California San Francisco UCSF, 94143 - San Francisco/US
  • 7-, Theradex Oncology, 08540 - Princeton/US
  • 8-, TAKARA BIO INC, Shiga/JP

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 were ≤G2, 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.

Clinical trial identification

NCT02272855.

Legal entity responsible for the study

TAKARA BIO INC

Funding

TAKARA BIO INC

Disclosure

R.H.I. Andtbacka: Receipt of grants/research supports: from Takara, Amgen, Viralytics Receipt of honoraria: from Merck, Novartis, M. Ross: Receipt of honoraria or consultation fees: AMGEN, MERCK, PROVECTUS Participation in a company sponsored speaker’s bureau: AMGEN, M. Taylor: Receipt of honoraria or consultation fees: Bristol Myers Squibb, Eisai Inc, Trillium Pharma, Blue Print Medicines. Participation in a company sponsored speaker’s bureau: Bristol Myers Squibb, Eisai Inc. J. Vetto: Receipt of grants/research supports: none Receipt of honoraria or consultation fees: Castle Biosciences, Novartis Participation in a company sponsored speaker’s bureau: Castle Biosciences, Amgen Stock shareholder (Yes/No): No Spouse/Partner (Yes/No): Yes; salary and stock (Roche)

All other authors have declared no conflicts of interest.