1104TiP - Intravenous coxsackievirus A21 in combination with pembrolizumab in advanced cancer patients: phase Ib KEYNOTE 200 study

Abstract

CAVATAKTM is a novel, bio-selected ICAM-1-targeted immunotherapeutic Coxsackievirus A21 (CVA21). Infection of the tumour micro-environment by CVA21 can increase levels of immune-checkpoint molecules, immune-cell infiltration and enhancement of systemic antitumour immune response. Pembrolizumab is a human programmed death receptor-1 (PD-1) blocking antibody that has induced responses in a number of tumour types via reversal of tumour-induced T-cell suppression. Preclinical studies in immune-competent mouse models of NSCLC and melanoma suggest combinations of IV CVA21 + anti-PD-1 mAbs mediate greater antitumour activity compared to single agent use. As such, we propose that the combination of CVA21 + pembrolizumab may translate to similar benefits in the clinic. The KEYNOTE 200 Phase Ib study (NCT02043665) assesses tolerance and efficacy of IV-delivered CVA21 ± pembrolizumab in advanced cancer pts. Trial design: Primary objectives are to assess dose-limiting toxicities (DLT) of CVA21 ± pembrolizumab. Secondary objectives include ORR by irRECIST criteria, PFS, and OS. Treatment: Part A: Pts are infused with CVA21 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 + 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. All subjects receive pembrolizumab at 200 mg IV Q3W from Day 8 for up to 2 years. Treatment with IV CVA21 ± pembrolizumab will continue until confirmed CR or PD (whichever comes first) per irRECIST or DLT. Key eligibility: Pts with advanced disease, lesion(s) accessible for core biopsy, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression. Clinical trial identification: NCT02043665 Legal entity responsible for the study: Viralytics Limited