CAVATAKTM is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21 (CVA21). In a phase 2 study, intratumoral (i.t.) CVA21 injection of advanced melanoma lesions with CVA21 resulted in increases in tumor immune-cell infiltration, up-regulation of ɣ-INF response and immune-checkpoint molecule genes, including CD122 which may be a potential prognostic factor for anti-tumor activity by anti-CTLA-4 blockade strategies. Presented are the preliminary data of the open-label, Phase Ib MITCI (Melanoma Intra-Tumoral Cavatak and Ipilimumab) study of novel immunotherapy combination CVA21 and ipilimumab in patients (pts) with advanced melanoma.
The Phase Ib MITCI study is investigating the efficacy and safety of i.t. CVA21 and i.v. ipilimumab in 26 pts with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts received up to 3 x 108 TCID50 CVA21 i.t. on study days 1, 3, 5, 8 and 22, and then q3w for a further 6 series of injections. Ipilimumab (3 mg/kg) q3w was given as 4 i.v. infusions starting at Day 22. The first response assessment (irWHO) occurred at study Day 106. The primary endpoint was to assess safety of CVA21 in combination with ipilimumab treatment (tx).
At present, of the 16 pts enrolled, no DLT's have been reported. Combination tx has been generally well-tolerated with only one Gr 3 or higher tx-related AE being ipilimumab-related fatigue. The study has met its primary statistical futility endpoint of achieving ≥ 4 confirmed objective responses (CR or PR) in the first 12 pts enrolled. Currently, of the first 7 pts eligible for investigator response assessment, ORR for the ITT population is 57.1% (4/7), with the ORR for ipilimumab-naïve pts being 67% (4/6). The DCR (CR + PR + SD) on the ITT population is currently 86% (6/7). All responses were observed by 3.5 mths with complete tumor responses being observed in individual injected and non-injected lesions.
Intratumoral CVA21 + ipilimumab tx of pts with advanced melanoma has been generally well tolerated. The combination immunotherapy tx has displayed anti-tumor activity in both local, visceral and non-visceral lesions in a number of patients that have failed previous lines of immunotherapy.
Clinical trial identification
Legal entity responsible for the study
B. Curti: Honoraria: Prometheus Clinical trial support; Prometheus Bristol-Myers Squibb MedImmune. J. Richards: Stock Ownership - Bristol-Myers Squibb (I). M. Faries: Served as an advisor or consultant for: Amgen Inc.; Astellas Pharma, Inc.; Genentech, Inc. R.H.I. Andtbacka: Consulting or Advisory Role - Amgen Speakers' Bureau - Novartis Research Funding - Amgen (Inst); Viralytics (Inst). M. Grose, R. Karpathy: Viralytics stock and employment at Viralytics. D. Shafren: stock ownership and CSO.