Intratumor injection of the oncolytic virus RP1 in combination with the checkpoint inhibitor nivolumab has demonstrated durable antitumor activity in patients with nonmelanoma skin cancer of the head and neck, according to data presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.¹ Results of the phase I/II IGNYTE trial showed durable clinical benefit in most patients who received the combination treatment, including responses in four different tumor types (cutaneous squamous cell carcinoma, angiosarcoma, Merkel cell carcinoma, and basal cell carcinoma).

Authors of the study also reported that tumor regression was observed in both injected and uninjected lesions, which is indicative of induction of a systemic immune response. The median duration of response has not been reached at the data cutoff.

“We are most excited about the remarkable complete response rate for cutaneous squamous cell carcinoma,” said Jiaxin Niu, MD, PhD, Co-Director of the Lung Cancer Program and Associate Director of the Head and Neck Cancer Program at Banner MD Anderson Cancer Center, Gilbert, Arizona. “Nearly 50% of the patients in this cohort achieved a complete response, which is unprecedented.”

Background and Study Details

As Dr. Niu explained, RP1 is an enhanced potency oncolytic herpes simplex virus 1 (HSV-1), which expresses fusogenic glycoprotein as well as granulocyte macrophage colony-stimulating factor (GM-CSF). Talimogene laherparepvec, a first-generation HSV-1 armed with GM-CSF, was the first oncolytic virus approved by the U.S. Food and Drug Administration to treat advanced melanoma and is routinely used in clinical practice.

“Oncolytic viruses have long been studied in cancer immunotherapy,” said Dr. Niu. “A bioengineered virus can preferentially infect and replicate in cancer cells to promote immunogenic cell death, and it can lead to activation of both innate and adaptive immunity.”

According to Dr. Niu, preclinical studies of RP1 demonstrated enhanced antitumor activity and immunogenic cell death.

This phase II portion of the open-label, multicenter, and multicohort IGNYTE study enrolled approximately 270 patients across five cohorts, including 30 patients with nonmelanoma skin cancer without prior exposure to PD-1 or PD-L1 treatment.

Eligible patients received an intratumor injection of RP1 (up to 10 mL) into one or more superficial and/or deep-seated, visceral lesions. Injections were followed by treatment with nivolumab for eight cycles, followed by nivolumab maintenance. Patients were eligible to receive additional doses of RP1 with or without nivolumab if they met protocol-specified criteria.

The primary objectives of the phase II portion are to assess the safety and overall response rate of the combination treatment. Secondary objectives include the duration of response, complete response rate, disease control rate, progression-free survival, as well as 1-year and 2-year survival rates.

Nearly 50% Complete Response Rate

Dr. Niu reported a particularly high rate of complete response in patients with cutaneous squamous cell carcinoma. Of the 15 patients enrolled in this cohort, 7 achieved a complete response.

When compared with studies of the immunotherapy cemiplimab-rwlc in cutaneous squamous cell carcinoma, which demonstrated a complete response rate of 7% to 15%, for example, Dr. Niu called the 47% complete response rate with RP1 plus nivolu­mab “striking” and “unprecedented.” Moreover, when partial responses and stable disease were included, up to 70% of patients with cutaneous squamous cell carcinoma achieved a clinical benefit from the combination therapy.

Rates of response were also encouraging in patients with angiosarcoma, Merkel cell carcinoma, and basal cell carcinoma, said Dr. Niu.

Safety Profile

The combination of intratumor injection of RP1 with checkpoint inhibition was also well tolerated. A few patients experienced flu-like symptoms, including mild fever and chills, which typically occurred after the first two injections. One patient also developed immune-mediated myocarditis, said Dr. Niu, but that was attributed to nivolumab.

Dr. Niu also underscored the feasibility of the injection process, which can be administered after 30 minutes of instruction.

“For superficial lesions, I give most injections myself,” he said. “For visceral lesions, however, interventional radiology may be needed to assist with ultrasound- or CT-guided injection.”

According to Dr. Niu, these data further support the ongoing registration-directed CERPASS clinical trial of RP1 combined with cemiplimab vs cemiplimab alone in cutaneous squamous cell carcinoma, where a “substantial proportion of patients would be expected to have disease of the head and neck.” 

Expert Point of View

Faye M. Johnson, MD, PhD, Professor, Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, called these preliminary results “very impressive.”

“The overall response rates were modestly higher than we would expect with anti–PD-1 therapy alone, and the complete response rates were much higher,” said Dr. Johnson in an interview with The ASCO Post. “If these responses are confirmed and durable, then RP1 plus nivolumab may be an excellent option for patients with advanced cutaneous squamous cell carcinoma who have injectable lesions.” 

DISCLOSURE: Dr. Niu reported financial relationships with Roche, OncLive, Boehringer Ingelheim, Merck, AstraZeneca, Blueprint Medicines, ImmVira, Johnson & Johnson, Takeda, Exelixis, BeiGene, and Mirati Therapeutics. Dr. Johnson reported no conflicts of interest.

REFERENCE

1. Niu J, Milhem M, Vanderwalde AM, et al: Safety and efficacy of RP1 + nivolumab in patients with non-melanoma skin cancer of the head and neck: Results from IGNYTE phase 1/2 multi-cohort clinical trial. 2022 Multidisciplinary Head and Neck Cancers Symposium. Abstract 12. Presented February 25, 2022.