658P - First-in-human phase I trial of oncolytic herpes simplex virus ONCR-177 alone or in combination with pembrolizumab in advanced solid tumors

Background

Oncolytic viruses have the potential to synergize with immune checkpoint inhibitors (ICI), especially when engineered to express immunomodulatory payloads. ONCR-177 is a next-generation oncolytic Herpes Simplex Virus-1 (oHSV-1) intended for intratumoral (IT) administration, developed to target solid tumors, in monotherapy and in combination with ICI.

Methods

A first-in-human phase 1 trial (NCT04348916) of IT ONCR-177 alone and in combination with pembrolizumab in patients (pts) with advanced cutaneous, subcutaneous or metastatic solid tumors (surface lesions), and liver metastases (visceral lesions) was performed. Primary objectives were safety, tolerability, and determination of the recommended Phase 2 dose (RP2D) of ONCR-177 alone and in combination with pembrolizumab. Secondary objectives were anti-tumor activity (RECIST v1.1), viral shedding and cytokine levels detection.

Results

A total of 66 pts, with a median age of 63, 55% females and with 13 different tumor types (most frequent breast cancer 30%) were enrolled (N=56 in surface and N=10 in visceral lesions cohort). Sixty-two pts were evaluable for safety. No dose-limiting toxicities (DLTs) were reported through different dose levels (DL) up to 4x10⁸ PFU in 4ml, which was defined as RP2D. The most common treatment-related adverse events (TRAEs) were cytokine release syndrome (CRS), in 14 pts (23%) or symptoms of fever, hypotension, and chills in 32 pts (52%). Only 1 pt had grade (G)3 CRS. Other TRAEs included G1/2 fatigue (37%). A total of 61 pts were evaluable for response, with 5 responders, all at RP2D and in surface lesions, 3 (5%) complete responses (CR) and 2 (3%) partial responses (PR), all previously exposed to ICI. Two CR were achieved in combination cohort. At RP2D, a trend towards higher plasma IFNγ levels and CRS-related AEs was observed, although no payload above physiologically relevant levels was detected.

Conclusions

ONCR-177 was safe to administer to surface and visceral lesions either as monotherapy or in combination with Pembrolizumab. Local responses were observed, although sustainable efficacy could not be achieved in a systemic manner in these heavily pretreated pts.

Clinical trial identification

NCT04348916.

Editorial acknowledgement

Legal entity responsible for the study

Oncorus.

Funding

Oncorus.

Disclosure

All authors have declared no conflicts of interest.