Tumor response from phase II study of combination treatment with intratumoral HF10, a replication-competent HSV-1 oncolytic virus, and ipilimumab in patients with stage IIIB, IIIC, or IV unresectable or metastatic melanoma

Date

09 Oct 2016

Session

Poster display

Presenters

Robert Andtbacka

Citation

Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379

Authors

R. Andtbacka1, M. Ross2, S.S. Agarwala3, M. Taylor4, J. Vetto4, R.I. Neves5, A. Daud6, H. Khong1, R.S. Ungerleider7, S. Welden7, M. Tanaka8, K. Grossmann1

Author affiliations

  • 1 Surgical Oncology, Huntsman Cancer Institute, 84112 - Salt Lake City/US
  • 2 Surgical Oncology, MD Anderson Cancer Center, Houston/US
  • 3 Cancer Center, St. Luke's Hospital & Health Network, 18015 - Bethlehem/US
  • 4 Knight Cancer Institute, Oregon Health Science University, Portland/US
  • 5 Surgical Oncology, Penn State Hershey Medical Center, Hershey/US
  • 6 Department Of Medicine (hematology/oncology), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco/US
  • 7 Clinical Operations, Theradex Oncology Experts, Princeton/US
  • 8 Project Management Dept, Takara Bio, Inc., Shiga/JP
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Background

HF10 is a replication-competent oncolytic virus derived from HSV-1. We report on the safety and preliminary antitumor activity of HF10 i.t. + ipilimumab (ipi) i.v. combination in an ongoing Ph2 trial in melanoma pts.

Methods

Entry criteria: age ≥18y, ECOG ≤ 2, Stage IIIB, IIIC or IV unresectable melanoma, ipi naïve and measurable non-visceral lesion(s) suitable for injection. HF10 was injected into single or multiple tumors (1x107 TCID50/mL/dose, up to 5mL based on tumor size and number); 4 inj qwk; then up to 15 inj q3wk. 4 ipi IV inf (3 mg/kg; + HF10) were administered q3wk. Tumor responses (mWHO & irRC) at 12, 18, 24wks, and at 36, 48wks for pts continuing on HF10 monotherapy. Primary endpoint is Best Overall Response Rate (BORR) at 24wks. DLTs defined as ≥G3 nonhematologic/hematologic toxicity, ≥G2 neurologic toxicity or allergic event occurring within 1st 3wks of therapy.

Results

Of 46 pts treated: 58% men; median age 68.4 yrs (range 29-92yrs); disease stage 20% IIIB, 43% IIIC and 37% IV. Of all patients, 49% with ≥1 prior cancer therapy. Of the 17 patients with stage IV, 25% had M1a, 31% M1b, 44% M1c. Majority of HF10-related AEs were ≤G2, similar to HF10 monotherapy and consistent with other oncolytic viruses. No DLTs reported. 4 G4 AEs reported, none were treatment-related. 30.4% of pts had G3 AEs. HF10-related G3 AEs (n = 3) were: left groin pain, a thromboembolic event and lymphedema; hypoglycemia; and diarrhea. Of 43 efficacy evaluable pts, preliminary BORR at 24 wks by irRC is 39.5% (11.6% CR, 27.9% PR), disease stability rate is 65.1% (25.6% SD). 8 responders (53%) were Stage IV. 5 responders (33%) were ≥2nd line. Overall study BORR, including those after 24 weeks, by irRC is 48.9% (14.0% CR, 34.9% PR), disease stability rate is 65.2% (16.3% SD). DCO = 10May16

Conclusions

The results indicate ipi + HF10 does not exacerbate ipi toxicity and the combination is safe and well tolerated. Preliminary efficacy evaluation suggests HF10 + ipi has both local and systemic antitumor activity and substantially improves the response rate of ipi alone. HF10 + ipi is a potential novel therapeutic approach for metastatic melanoma.

Clinical trial identification

NCT02272855

Legal entity responsible for the study

Takara Bio Inc

Funding

Takara Bio, Inc

Disclosure

R. Andtbacka: Has been recipient of honoraria or consultation fees from Amgen, Merck, Provectus. M. Ross: Grants/Research Supports: GSK, Amgen, Merck, Provectus Honoraria or Consultation Fees: Amgen, GSK, Merck Travel Expenses: GSK, Amgen, Merck, Provectus, Caladrius. M. Taylor: Has received honoraria for consultation from Onyx and Eisai. A. Daud: Receipt of grants/research supports: Merck, Oncosec, BMS, GSK Receipt of honoraria and consultation fees: Merck, Oncosec. H. Khong: Received grant and research support: Celgene, BMS, AstraZeneca. M. Tanaka: Works at Takara Bio Inc, the sponsor for the study. K. Grossmann: Receipt of honoraria or consultation fees: Genentech and Castle Biosciences. All other authors have declared no conflicts of interest.

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