A presentation at the American Society of Clinical Oncology (ASCO) 2022 Annual meeting, which was held 3-7 June 2022, in Chicago, IL, described the CERPASS trial in progress (NCT04050436). CERPASS is testing whether adding an enhanced potency oncolytic herpes simplex virus 1 (HSV-1) that expresses a fusogenic glycoprotein and granulocyte macrophage colony stimulating factor (collectively called RP1) can improve the efficacy of PD-1 inhibitor cemiplimab in patients with advanced or metastatic cutaneous squamous cell carcinoma (CSCC). The presenting author was Dr. Andrew Mark Haydon (Monasch University, Melbourne, Australia) [1].

Dr. Haydon told Physician’s Weekly:

Cutaneous squamous cell carcinoma (CSCC) is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. The unmet need CERPASS is trying to address is that the prognosis for advanced and metastatic CSCC remains poor for many patients with the disease despite approval of the immune checkpoint inhibitors cemiplimab and pembrolizumab [2,3]. We know from preclinical studies that RP1 can induce immunogenic tumor cell death with consequent systemic anti-tumor activity, which can be further amplified by combining RP1 with anti-PD-1 checkpoint inhibition agents [4]. Intirim findings from the phase 1/2 IGNYTE trial, testing RP1 in combination with nivolumab in patients with CSCC, showed promising antitumor activity [5]. Cemiplimab is currently indicated for the treatment of metastatic or locally advanced CSCC in patients who are not candidates for curative surgery or curative radiation and was therefore selected as the checkpoint inhibitor in this study, which will complement IGNYTE. It is also indicated in the treatment of locally advanced or metastatic basal cell carcinoma (BCC) in patients previously treated with a hedgehog inhibitor or for whom hedgehog inhibitor therapy is not appropriate. The safety profile of cemiplimab is quite manageable for most patients. The CERPASS trial aimed to evaluate whether the addition of RP-1 could enhance the efficacy of cemiplimab in advanced or metastatic CSCC, without adding significant safety risks.

CERPASS is a global, multicenter, randomized phase 2 study enrolling patients with metastatic or unresectable, locally advanced CSCC who are not candidates for/refuse surgery and/or radiotherapy. We hope to enroll 180 patients. To be eligible, patients should have never received prior treatment with anti-PD1/PD-L1 checkpoint inhibitor agents or oncolytic viruses. Patients are being randomized in a 2:1 ratio for the RP1 + cemiplimab arm versus cemiplimab monotherapy, respecitively. Participants in the cemiplimab monotherapy arm will receive 350 mg of cemiplimab intravenously every 3 weeks for up to 108 weeks. Participants in the combination arm will be injected intratumorally at a starting RP1 dose of 1 × 10^6 plaque forming units (PFU)/mL alone, followed by up to 7 doses of RP1 at 1 × 10^7 PFU/mL Q3W together with cemiplimab. Patients in the combination arm may receive up to 8 additional RP1 doses. There is no crossover between the arms allowed.

Although we are still enrolling patients, we are assessing tumor size every 9 weeks. Primary endpoints are overall response rate and complete response rate by blinded independent review. Secondary endpoints include safety, progression-free survival, duration of response, and overall survival. Exploratory endpoints include viral shedding and biodistribution, and immune biomarker analyses. We anticipate that a substantial proportion of patients will come from the head and neck population, just like the original cemiplimab study—in that cohort 60% of tumors arose from the head and neck region.

Of course, the results are not yet known, but we hope that this trial will offer some clarity about a synergistic effect of oncolytic virus therapy with a backbone of immune checkpoint inhibition, without compromising safety.