Abstract CT121: A phase Ib study of recombinant vaccinia virus in combination with immune checkpoint inhibition (ICI) in advanced renal cell carcinoma (RCC)
Authors: Rha Sun Young , Merchan Jamie , Oh Sung Yong , Kim Chan , Bae Woo Kyun , Lee Hyun Woo , Dillon Myles , Deering Raquel , Kroog Glenn , Ha Kyoung Soo 
Published: September 2020

Abstract
Background: Oncolytic immunotherapy employs viruses that are designed to preferentially replicate in and lyse cancer cells and in this process trigger anti-tumor immunity. Pexa-Vec (Pexastimogene Devacirepvec) is an oncolytic and immunotherapeutic vaccinia virus engineered to express GM-CSF. REN026 is a clinical trial of Pexa-Vec in combination with cemiplimab (REGN2810, anti-PD-1) in patients with metastatic or unresectable RCC. Depending upon the cohort, Pexa-Vec is administered either via intravenous (IV) infusion or intratumoral (IT) injection. Initial data from dose-escalation and expansion cohort C are reported here. Methods: Patients with histologically confirmed metastatic or unresectable clear cell RCC patients, naïve or refractory to prior systemic treatment, without prior treatment with immune checkpoint inhibitor were recruited. In dose-escalation cohort of the 3+3 design, patients were treated with 3 x 108 or 1 x 109 plaque forming unit (pfu) of 4 weekly intravenous (IV) infusion of Pexa-Vec starting at Day -7 plus cemiplimab (350 mg every 3 weeks) from Day 1. Radiographic assessments per RECIST 1.1 were performed centrally every 9 weeks from Day 1. Upon determination of the recommended phase Ib dose of 1 x 109 pfu of Pexa-Vec IV, expansion cohort C recruited 11 patients to assess if 3 or more responses were observed at the interim analysis to expand the cohort. Results: The escalation cohort and expansion cohort enrolled 6 and 11 patients respectively with a median age of 62 (44-77). 3 patients were systemic treatment naïve. 12 out of 16 evaluable (75%) patients showed tumor burden reduction of whom 9 had ≥30% tumor burden reduction. The best overall responses (BOR) in 16 evaluable patients was 37.5% (1 complete response and 5 partial response). 6 patients (37.5%) had stable disease and 4 (25%) progressive disease as their best response. The disease control rate (DCR) was 75%. Up to 27 weeks from the Day 1, 5 (43.8%) patients progressed by RECIST criteria. There were 4 confirmed responses (36%) in expansion cohort C. Overall, 12 out of total 210 adverse events (5.7%) were reported as CTCAE Grade 3, which includes fever, flu-like symptom, blood pressure change post infusion and pneumonia, which are mostly transient. 7 patients (41%) experienced at least one G3 event. Correlations between Pexa-Vec-induced anti-Vaccinia and anti-tumor T cell responses with tumor regression are currently being assessed. Conclusions: A cohort of patients in the REN026 study with advanced renal cell carcinoma may benefit from IV Pexa-Vec + cemiplimab with an acceptable safety profile. Further investigation is on-going with additional patients in stage 2 of expansion cohort C and another cohort with IT Pexa-Vec + cemiplimab. A newly added Cohort D of patients who progressed on previous immune checkpoint inhibition is to be opened soon. Clinical trial information:NCT03294083
Citation Format: Sun Young Rha, Jamie Merchan, Sung Yong Oh, Chan Kim, Woo Kyun Bae, Hyun Woo Lee, Myles Dillon, Raquel Deering, Glenn Kroog, Kyoung Soo Ha. A phase Ib study of recombinant vaccinia virus in combination with immune checkpoint inhibition (ICI) in advanced renal cell carcinoma (RCC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT121.