The MITCI (Phase 1b) study. A novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients with or without previous immune checkpoint therapy treatment.
B. Curti S. Hallmeyer J. Richards R. Andtbacka M. Faries G. Daniels M. Grose D. Shafren
Background
CAVATAK 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 resulted in increases in tumor immune-cell infiltration, up-regulation of γ-INF response and immune-checkpoint genes, including CD122 which may be a potential prognostic marker for enhanced anti-tumor activity by anti-CTLA-4 blockade strategies.
Methods
The Phase Ib MITCI study (NCT02307149) is investigating the efficacy and safety of i.t. CVA21 and i.v. ipilimumab in up to 70 pts with treated or untreated unresectable Stage IIIB-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.
Results
At present no DLT’s have been reported in the 30 pts currently enrolled. Combination treatment has been generally well-tolerated with surprisingly only two Gr 3 or higher treatment-related AE being ipilimumab-related fatigue and elevated liver enzymes. Currently, of the first 23 pts eligible for investigator response assessment, the confirmed ORR for the ITT population is 48.0% (11/23), with the ORR for immune checkpoint-naïve pts being 64% (7/11) and previous immune checkpoint therapy pts being 33% (4/12). Of note, is the encouraging ORR of 50% (4/8 pts) in pts with stage IVm1c disease. The DCR (CR+PR+SD) on the ITT population is currently 74% (17/23) of which > 66% of patients have been administered prior systemic therapy(s) with DCR of 88% (7/8) in pts with stage IVm1c disease.
Conclusions
Treatment of pts with CVA21 and ipilimumab has demonstrated durable response with minimal toxicity. The combination immunotherapy treatment has displayed anti-tumor activity in local, visceral and non-visceral lesions. Finally, responses are observed in patients with disease progression following immune checkpoint inhibitor therapy, suggesting the additive therapeutic benefit of CVA21 with ipilimumab.
Clinical trial identification
NCT02307149
VLA Price at posting:
90.0¢ Sentiment: Buy Disclosure: Held
