Phase I Storm Study (Keynote 200): Intravenous Delivery Of A Novel Oncolytic Immunotherapy Agent, Coxsackievirus A21 In Combination With Pembrolizumab In Advanced Cancer Patients

TPS3108 Background: Coxsackievirus A21 (CVA21, CAVATAK) is a naturally occurring ICAM-1 targeted oncolytic immunotherapeutic virus. Tumor infection by CVA21 can increase levels immune-checkpoint molecules, immune-cell infiltration and enhancement of systemic antitumor immune response. Pembrolizumab is a human programmed death receptor-1 (PD-1) blocking antibody that has yielded significant solid tumor responses via reversal of tumor induced T-cell suppression. Preclinical studies in an immune-competent mouse model of melanoma confirmed that combinations of IV CVA21 + anti-PD-1 mAbs mediated significantly greater antitumor activity compared to use of either agent alone. We postulate that the combination of CVA21+pembrolizumab may translate to a similar benefit in the clinic. We describe a Phase I study assessing safety and efficacy of IV CVA21 ± pembrolizumab in advanced cancer pts. Methods: The Phase I STORM: Systemic Treatment Of Resistant Malignancies: NCT02043665 (KEYNOTE 200): Primary objectives are to assess dose-limiting toxicities (DLT) of CVA21 ± pembrolizumab. Secondary objectives are to assess ORR as by irRECIST 1.1 criteria, PFS, and OS. Treatment: Part A: Pts are infused with CVA21 in 100 mL saline in Cohort 1 (n = 3), at a dose of 1 x 108 TCID50 , in Cohort 2 (n = 3) at a dose of 3 x 108 TCID50 and in Cohort 3 (n = 12-18) at a dose of 1 x 109 TCID50 on study days 1,3,5,22 and Q3W for 6 additional infusions. Part A enrollment is almost complete. Part B: Pts are infused with CVA21 in 100 mL saline + pembrolizumab. In Cohort 1 (n = 3), CVA21 is administered at a dose of 1 x 108 TCID50 , in Cohort 2 (n = 3) at a dose of 3 x 108 TCID50 and in Cohort 3 (n = ~80) at a dose of 1 x 109 TCID50 on study days 1,3,5,8,29,and Q3W for 6 additional infusions. Pembrolizumab is given in all cohorts at 200 mg IV Q2W from Day 8 for up to 2 years. Treatment with CVA21 ± pembrolizumab will continue until confirmed CR or PD (whichever comes first) per irRECIST 1.1 or DLT. Key eligibility: Pts with advanced disease considered appropriate treatment with CVA21 ± pembrolizumab, lesion(s) accessible for core biopsy, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression. Clinical trial information: NCT02043665.