— Multi-center dose escalation and expansion study will assess safety, tolerability and preliminary efficacy of treatment with ONCR-177 alone and in combination with Merck’s KEYTRUDA® (pembrolizumab) —
— Planned expansion cohorts to include patients with breast cancer, squamous cell carcinoma of the head and neck (SCCHN), and melanoma —
— Intratumorally administered oncolytic Herpes Simplex Virus (oHSV) viral immunotherapy engineered with multiple proprietary mechanisms to enhance potency while ensuring safety —
— Six immuno-oncology approaches in one (oHSV, IL-12, CCL4, FLT3LG, anti-PD-1 and anti-CTLA-4) designed to stimulate multiple arms of the immune system; Orthogonal safety strategies to retain full replication competency and allow for replication only in tumor tissues —
CAMBRIDGE, Mass., July 16, 2020 – Oncorus, Inc., a viral immunotherapies company focused on driving innovation to transform outcomes for cancer patients, today announced that it has initiated a Phase 1 study of its lead product candidate, ONCR-177, an intratumorally administered oncolytic Herpes Simplex Virus (oHSV) viral immunotherapy being developed for multiple solid tumor indications. The Phase 1 open-label, multi-center, dose escalation and expansion study is designed to evaluate the safety and tolerability and to determine the recommended Phase 2 dose as well as preliminary anti-tumor activity of ONCR-177 alone and in combination with Merck’s anti-PD1-1, KEYTRUDA® (pembrolizumab), in patients with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors.
“Initiating our first-in-human study of ONCR-177 is a significant milestone, bringing us a major step closer to delivering on our mission to realize the full promise of viral immunotherapy for cancer patients across multiple indications, including some of the most notoriously difficult-to-treat types of cancer,” said Theodore (Ted) A. Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. “Our oHSV Platform represents a potential breakthrough for the viral immunotherapy class due to the multiple proprietary innovations our team has developed to activate multiple arms of the immune system to enhance potency while balancing safety.”
Dr. Ashburn continued, “A huge thank you to our team and collaborators for their tremendous effort preparing for this study amidst the unprecedented challenges presented by the COVID-19 pandemic. I’m proud and honored to work with such a bright, dedicated and patient-driven group of people.”
“While we have seen great success with immuno-oncology as an approach in some patients, these therapies have not benefited all patients with cancer and new strategies are needed,” said Shiraj Sen, M.D., Ph.D., Associate Director, Drug Development Unit, Sarah Cannon Research Institute at HealthONE in Denver, Colorado. “Given its differentiated profile, ONCR-177 has the potential to enable more patients to respond to, and realize the benefits of, immuno-oncology treatment. We are pleased to be part of this important first-in-human study of this next-generation viral immunotherapy.” Dr. Sen is a site investigator for the ONCR-177 Phase 1 study, and his site enrolled and dosed the first patient in this trial.
John Goldberg, M.D., Senior Vice President of Clinical Development at Oncorus, commented, “We are privileged to be working with preeminent cancer research institutions and leading researchers on the execution of this study. We are also thrilled to enter a clinical collaboration with Merck to study ONCR-177 in combination with KEYTRUDA, which is a key component of the trial. Above all, we are humbled to now be in a study in patients with ONCR-177 and believe in its potential to become a foundational component of oncologists’ anti-tumor arsenal. Our team is motivated by the courage of cancer patients and driven to enable every patient to win their war against this disease.”
Oncorus has designed its proprietary oHSV Platform to develop improved intratumorally administered viral immunotherapies that have the potential to enhance potency without sacrificing safety, a challenge that has been encountered by earlier generation programs in this class. ONCR-177 is designed to mount a powerful, multidimensional attack on cancer; it induces immunogenic cancer cell death and ignites innate and adaptive immunity to drive a lasting and systemic anti-tumor response. In addition to its oncolytic activity, ONCR-177 is armed with five immunomodulatory transgenes: IL-12, CCL4, FLT3LG, and antagonists of clinically proven immune checkpoints PD-1 and CTLA-4. This represents a greater payload capacity than viral immunotherapies that are either currently approved or in clinical development.
In preclinical studies, ONCR-177 was shown to stimulate multiples arms of the immune system, drive abscopal activity and prolong survival while limiting systemic exposure to transgene products, such as IL-12, that generally cannot be safely dosed systemically due to toxicities.
ONCR-177 retains full replication competency to enable potent tumor cell killing. It also incorporates two highly innovative approaches — the use of microRNA target sequences and a proprietary mutation engineered in an HSV-1 protein, known as UL37 — to allow for tumor-specific replication, which restricts viral activity to tumor cells while sparing normal tissues.
About the Phase 1 ONCR-177 Study
The first part of the study involves a monotherapy dose escalation of ONCR-177 and will enroll approximately 21 cancer patients with advanced or metastatic solid tumors for whom surgical resection or locoregional therapy is not indicated, and who are refractory to, ineligible for, relapsed from and/or intolerant of standard of care treatment or have a disease for which no standard of care exists. The Phase 1 trial will escalate the dose of ONCR-177 until the recommended phase 2 dose is determined.
Upon determination of the recommended Phase 2 dose, the study will then enroll patients to histology- specific expansion cohorts to demonstrate safety and initial efficacy of ONCR-177 as a monotherapy and in combination with KEYTRUDA, in addition to enabling biomarker exploration. The expansion cohorts will enroll patients with solid tumors who are refractory to, ineligible for, relapsed from and/or intolerant of standard of care treatment or have a disease for which no standard of care exists, including patients with breast cancer, squamous cell carcinoma of the head and neck (SCCHN), and melanoma.
For more information on the study, please visit: https://clinicaltrials.gov/ct2/show/NCT04348916.
At Oncorus, we are focused on driving innovation to deliver next-generation viral immunotherapies to transform outcomes for cancer patients. We are advancing a portfolio of intratumorally and intravenously administered viral immunotherapies for multiple indications with significant unmet needs based on our oncolytic Herpes Simplex Virus Platform and Synthetic Virus Platform. Please visit www.oncorus.com to learn more.