In 2019, Cancer Therapy Advisor reported on the failed phase 3 trial of the vaccinia virus (VV) pexastimogene devacirepvec (Pexa-Vec) plus sorafenib for hepatocellular carcinoma (HCC). The PHOCUS trial, as it was known, was a culmination of years of promising translational and earlier-phase trials showing benefits with Pexa-Vec in combination with an immune checkpoint inhibitor (ICI).1 Although the phase 3 results in HCC did not deliver, early-phase trials continue to investigate this therapeutic combination in other tumor types, including renal cell carcinoma (RCC).

Last month, Sun Young Rha, MD, PhD, chief of medical oncology at Yonsei University College of Medicine in Seoul, South Korea, presented results from a phase 1b study of Pexa-Vec plus cemiplimab (a programmed death receptor-1 [PD-1] inhibitor) in patients with advanced RCC.2 These results were included among the “high-impact” presentations selected for part 1 of the 2-part American Association for Cancer Research (AACR) Virtual Annual Meeting 2020.

Dr Rha and colleagues tested Pexa-Vec2 in patients with histologically confirmed metastatic or unresectable clear cell RCC (ccRCC; ClinicalTrials.gov Identifier: NCT03294083). All patients had measurable lesions, were either treatment-naive or refractory to systemic treatment, and had not received prior treatment with an ICI.3

Part 1 of the study evaluated the dose escalation of Pexa-Vec between 3 x 108 and 1 x 109 plaque-forming units (pfu) to determine the recommended dose. Six patients were enrolled to receive 4 weekly intravenous (IV) infusions of Pexa-Vec (starting day -7) and 3 weekly doses of cemiplimab 350 mg (starting day 1). Results, after 9 weekly radiographic assessments based on RECIST 1.1 criteria, showed that the preferred IV dose of Pexa-Vec was 1 x 109 pfu.3


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From there, the study opened expansion cohort C, recruiting 11 ICI-naive patients to receive IV Pexa-Vec plus cemiplimab. If 3 or more patients showed a response in the interim analysis, the investigators would expand the cohort. At AACR, Dr Rha reported2 initial data from part 1 and cohort C, in which the median patient age was 62 years (range, 44-77 years), and 3 individuals were naive to systemic treatment.3

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Results showed a reduction in tumor burden in 75% of evaluable patients (12/16), three-quarters of whom had at least a 30% reduction in tumor burden.In addition, Dr Rha and colleagues reported: “The best overall responses (BOR) in 16 evaluable patients was 37.5% (1 complete response and 5 partial response[s]) … 6 patients (37.5%) had stable disease and 4 (25%) [had] progressive disease as their best response. The disease control rate (DCR) was 75%.”3

After 27 weeks of follow-up, 44% of patients met RECIST criteria for disease progression. Four patients (36%) from cohort C had a confirmed response. As for safety, less than 6% of all adverse events were grade 3 Common Terminology Criteria for Adverse Events (CTCAE), most of which were transient; 7 of the 16 (41%) patients had at least 1 grade 3 adverse event.3

Given these positive results in advanced RCC (albeit in initial phase 1b data), why are we seeing different outcomes with VV plus ICI across different tumor types (eg, HCC and RCC)? It could come down to immunosuppression in the tumor environment, some experts hypothesize.