Presentation Abstract Abstract Number: CT021 Presentation Title:...

Presentation Abstract

Abstract Number: CT021
Presentation Title: Phase Ib study of a novel immunotherapy combination therapy of intralesional coxsackievirus A21 and systemic ipilimumab in patients with advanced melanoma
Presentation Time: Monday, Apr 18, 2016, 8:00 AM -12:00 PM
Location: Section 13
Poster Board Number: 2
Author Block: Brendan Curti1, Jon Richards2, Mark Faries3, Mark Grose4, Roberta Karpathy5, Darren R. Shafren5.1Providence Cancer Center, Portland, OR;2Oncology Specialists, Chicago, IL; 3John Wayne Cancer Institute, Santa Monica, CA; 4Viralytics Limited, Sydney, Australia; 5Viralytics Limited, New Lambton, Australia
Abstract Body: Background: CVA21 (CAVATAK) is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21. Intratumoral (i.t.) CVA21 injection can induce preferential tumor cell infection, tumor immune-cell infiltration, up-regulation of γ-INF response genes, cell lysis and enhancement of a systemic anti-tumor immune response. Pre-clinical studies in an immune-competent mouse model of melanoma have revealed that combinations of intralesional CVA21 and anti-CTLA-4 or anti-PD-1 mAbs mediated significantly greater antitumor activity and compared to use of either agent alone. Presented are the interim data of the open-label, multicenter Phase Ib MITCI (Melanoma Intra-Tumoral Cavatak and Ipilimumab) study of novel immunotherapy combination Coxsackievirus A21 and ipilimumab in patients with advanced melanoma
Methods: The Phase Ib MITCI study (NCT02307149) is investigating the efficacy and safety of i.t. CVA21 and i.v. ipilimumab in 26 patients with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts received up to 3 x 10e8 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. Treatment is continued until DLT, intolerance, all injectable tumors disappeared, or confirmed disease progression (PD) per immune-related (ir) WHO response criteria. The first response assessment occurs at study Day 106. Key eligibility criteria were ≥ 18 yrs old, ECOG PS 0-1, and at least 1 injectable cutaneous, subcutaneous, or nodal melanoma metastasis ≥ 1.0 cm. The primary endpoint was to assess safety of CAVATAK in combination with scheduled ipilimumab treatment. Secondary endpoints included irWHO objective response rate (ORR), responses in injected and non-injected lesions, durable response rate (continuous response ≥ 6 mos), median time to initial response, survival and QOL.
Results: At present, of the 7 patients enrolled, no DLT’s have been reported. Combination treatment has been generally well-tolerated with only 2 Gr 3 AEs reported, one with ipilimumab-related fatigue and the other with unrelated hypertension. Of 5 pts with investigator assessed response, ORR was 80%, with all responses occurring by 3.5 months and in both injected and non-injected lesions. Responses were observed in patients with Stage IIIC and Stage IV M1a/c disease. Response rates in individual injected and non-injected lesions were 80% (n=10) and 87% (n=15), respectively. Complete tumor responses were observed in some visceral and non-visceral lesions. Patients developed notable levels of anti-CVA21 serum neutralizing antibody by Day 22.
Conclusions: Intralesional CVA21 + ipilimumab is a promising novel oncolytic immunotherapeutic combination for the treatment of unresectable Stage IIIC-IVM1c melanoma. At present no DLT has been achieved, with no Gr 3/4 CVA21-related AEs observed. The preliminary overall response rate (80%) is higher than published rates for either agent used alone (CVA21: 28.1% and ipilimumab:~15-20%) in advanced melanoma patients. The combination immunotherapy treatment is generally well tolerated and has displayed antitumor activity in both local and systemic disease, also within environments of high levels of anti-CVA21 serum neutralizing antibody.