Abstract C111: Safety profile and tumor response in patients with refractory superficial cancers treated with HF10, an oncolytic replication-competent HSV-1-derived intratumoral injectable, as monotherapy and combined with ipilimumab
Authors: Andtbacka Robert H.I. , Grossmann Kenneth F. , Khong Hung T. , Tanaka Maki , Ungerleider Richard S. , Boran Aislyn D. , Ferris Robert L. 
Published: May 2016

Abstract
Background:
Here, we report on safety, recommended HF10 dose, viral shedding in body fluids and overall (all target lesions) and local (injected lesion) antitumor activity in patients (pts) with superficial tumors (13 squamous cell carcinoma, 9 malignant melanoma and 4 other tumor types) in a Phase 1 monotherapy study. In addition, we report on preliminary safety data and antitumor activity of HF10 + ipilimumab combination in an ongoing Phase 2 trial in pts with unresectable or metastatic melanoma.
Methods:
In Stage 1 of the Phase 1 study, a single HF10 injection was administered to a superficial/cutaneous lesion; in Stage 2, up to 4 injections (≥ 2 weeks apart) were given. Adverse events (AEs) were assessed per CTCAE 3.0. Tumor responses were assessed per RECIST 1.0.
In the ongoing Phase 2 study, HF10 is injected into single or multiple tumors (at 1 × 107 TCID50/mL, up to 5mL depending on tumor size and number); 4 injections at 1-week intervals; then up to 15 injections at 3-week intervals. Four ipilimumab IV infusions (3 mg/kg; concurrent with HF10) are administered at 3-week intervals. AEs are assessed per CTCAE 4.0. Tumor responses are assessed per mWHO and irRC.
Results:
Of 26 pts treated in the Phase 1 study, 24 pts had AEs. Nine (35%) pts had HF10-related AEs including chills (n = 3), fatigue (n = 2) and injection site reactions (n = 6). There were no ≥ Grade 3 (G3) HF10-related AEs. HF10 was rapidly cleared from blood, saliva and urine. Pt HSV-1 serostatus did not affect AE profile or HF10 clearance. Of 24 evaluable pts at end of study (EOS; ≥ 10 wks after start of HF10), none had complete (CR) or partial response; 7 had local stable disease (SD); 8 had overall SD, and 6 of 9 melanoma pts had overall SD. Although there were no partial responders per RECIST, but 1 melanoma pt had a 45% decrease in injected tumor size and another melanoma pt had 3 uninjected lesions disappear, despite overall SD. In long-term follow-up after EOS, 3 other melanoma pts had delayed responses in HF10-injected lesions: 1pt with an injected thigh tumor had pathological CR on resection and remains disease free 1.5 yrs later, 1 pt with an injected submandibular lymph node (LN) had CR and remains disease free, and 1 pt had CR in an injected neck LN, but has slowly progressed in a lung metastasis. None of these 3 pts received any additional treatment after completing HF10 injections.
In the ongoing Phase 2, 24 pts have been treated and HF10-related AEs reported thus far are similar to those previously reported for HF10 monotherapy and none are ≥ G3. Of note, the commonly reported ≥ G3 immune-mediated ipilimumab-related events of colitis, hepatitis and endocrinopathies have not been observed. Four efficacy evaluable and 2 pts on-study &lt; 12 wks (not yet evaluable) are showing a decrease in lesion size in response to treatment, with 2 documented local CRs.
Conclusions:
Intratumoral HF10 serial injections are safe and well-tolerated, in monotherapy (Phase 1) and in combination with ipilimumab (preliminary Phase 2). HF10-related AEs include chills, fatigue and injection site reactions. Efficacy evaluation (overall and local) suggests that HF10 has both local and systemic antitumor activity in melanoma and can result in delayed responses. Assessment of HF10 as a potential new treatment for melanoma pts is ongoing in a Phase 2 study.
Citation Format: Robert H.I. Andtbacka, Kenneth F. Grossmann, Hung T. Khong, Maki Tanaka, Richard S. Ungerleider, Aislyn D. Boran, Robert L. Ferris. Safety profile and tumor response in patients with refractory superficial cancers treated with HF10, an oncolytic replication-competent HSV-1-derived intratumoral injectable, as monotherapy and combined with ipilimumab. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C111.