Trial Outcomes & Findings for A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma (NCT NCT03294083)

Patients with histologically or cytologically confirmed metastatic or unresectable clear cell Renal Cell Carcinoma (RCC) were recruited for this study. The recruitment took place at 17 study centers across the United States, South Korea, and Australia. The first patient was enrolled on June 19, 2018, and the last patient completed the study on February 16, 2023. It was noted that there were some recruitment limitations due to intratumoral injection constraints.

A total of 141 patients were screened for eligibility prior to group assignment, which included 8 patients for Part 1 and 133 patients for Part 2. Of these, 46 patients failed the screening process (2 patients in Part 1 and 44 patients in Part 2). Consequently, a total of 95 eligible patients were enrolled and assigned to the study groups (6 patients in Part 1 and 89 patients in Part 2).

The number of participants analyzed for this baseline measure is lower than the overall number of enrolled participants in each arm because valid baseline tumor size measurements per Central Radiologic Review (Central RECIST 1.1) were not available or evaluable for all enrolled participants.

Safety will be determined by assessing the incidence, severity, and frequency of all treatment-emergent adverse events (TEAEs), Grade 3 or greater AEs, serious adverse events (SAEs), laboratory toxicity, AEs requiring discontinuation of study agent(s), and deaths. The severity of all adverse events and laboratory abnormalities is assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Safety is monitored from the first dose throughout the treatment period (up to a maximum of 1 year) and up to 28 days after the last dose of study treatment.

Overall response rate (ORR) is defined as the proportion of patients whose best overall responses either complete response (CR) or partial response (PR). The best overall response is the best response recorded from the randomization until disease progression. Proportions of patients with a best overall response of CR, disappearance of all target tumors; or PR, at least 30% decrease in the sum of longest diameter of target tumors will be presented by treatment arm along with exact 95% CIs. Analyses will be performed based on central assessments using RECIST v1.1.

Dose-limiting toxicity (DLT) was assessed to determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of Pexa-Vec. Patients were observed for DLTs during the IV treatment phase through Day 29. DLTs are evaluated based on the severity and frequency of adverse events and laboratory abnormalities using NCI CTCAE Version 5.0.

Defined as the date of the first study treatment to the date of first documented radiographic tumor progression or death due to any cause, whichever occurs first (RECIST v1.1). Progression free survival will be presented descriptively using Kaplan-Meier curves. Summary statistics from the Kaplan-Meier distributions will be determined, including median PFS and 25% and 75% quartiles with corresponding 95% CIs. The proportions of patients.

Defined as the proportion of patients whose best overall response is either complete response (CR), partial response (PR), or stable disease (SD). (RECIST v1.1)

Overall survival is defined as the time from first study treatment until death from any cause. For patients not known to have died at the time of the analysis, overall survival will be censored on the date they were last known to be alive. If a patient withdraws early, overall survival will not be censored at the date of withdrawal unless this is the date they were last known to be alive. Date of death will be obtained from the death certificate (preferable) or from a written statement from the primary care or attending physician, or from death registry data. Additionally, for censored date, the latest date of (in the following order): End of Treatment visit(EOT) / Last Radiologic Timepoint(LastRTP) / End of Study(EOS) / Last Drug Date(D.LastDrug) / before cutoff date(2023-02-16) is the censored date.