Keynote-200 phase 1b: A novel combination study of intravenously delivered coxsackievirus A21 and pembrolizumab in advanced cancer patients.

Abstract

TPS3108 Background: Coxsackievirus A21 (CVA21, CAVATAK) is a naturally occurring ICAM-1 targeted oncolytic immunotherapeutic virus. 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. Intravenous (i.v.) CVA21 mono-therapy is generally well tolerated, with low toxicity and can successfully target tumors in patients with melanoma, NSCLC and bladder cancer as confirmed by detection of CVA21 viral RNA in post-treatment tumor biopsies (Pandha et al., 2016). Intratumoral CVA21 replication has the potential to up-regulate numerous key immune checkpoint molecules, including PD-L1 (Andtbacka et al., 2016).The combination of i.v. CVA21+pembrolizumab may translate to a potential enhanced benefit in the clinic. Methods: The Phase Ib KEYNOTE-200 (NCT02043665) Treatment: Primary objectives are to assess dose-limiting toxicities (DLT) of CVA21 in combination with pembrolizumab. Secondary objectives are to assess ORR by irRECIST 1.1 criteria, PFS, and OS. Patients (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 Q3W from Day 8 for up to 2 years. Treatment (tx) with CVA21 + pembrolizumab will continue until confirmed CR or PD (whichever comes first) per irRECIST 1.1 or DLT.To date the combination of intravenous CVA21 and pembrolizumab has been generally well-tolerated. At present one gr 3 CVA21-related hyponatremia with no DLT for the combination of CVA21 and pembrolizumab being observed. Enrolment in Cohorts 1 and 2 is complete with tx of pts in Cohort 3 currently underway. Key eligibility: Pts with advanced disease considered appropriate tx with CVA21 + pembrolizumab, lesion(s) accessible for core biopsy, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression. Clinical trial information: NCT02043665.