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

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 1^st 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 ≥2^nd 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.