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

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Cancer Immunology and Immunotherapy
Presenter Hardev Pandha
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors H.S. Pandha1, K. Harrington2, C. Ralph3, A. Melcher4, E. Schmidt5, D.R. Kaufman6, M. Grose7, R. Karpathy7, D. Shafren7
  • 1Oncology, University of Surrey, GU2 7WG - Surrey/GB
  • 2Division Of Radiotherapy And Imaging, The Institute of Cancer Research and Royal Marsden Hospital, SW7 6JB - London/GB
  • 3St. James's Institute Of Oncology, University of Leeds, Leeds/GB
  • 4Oncology And Clinical Research, Leeds Institute of Cancer and Pathology, Leeds/GB
  • 5Clinical, Merck Co, Kenilworth/US
  • 6Oncology Clinical Research, Merck & Co., Inc., Kenilworth/US
  • 7Viralytics, Viralytics Limited, Sydney/AU

Abstract

Background

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

Funding

Viralytics Limited

Disclosure

H.S. Pandha: Research Funding - Viralytics Limited Travel, Accommodations, Expenses – Viralytics. K. Harrington: Honoraria - Amgen; Celgene; Merck Sharp & Dohme; Oncos Therapeutics Consulting - Amgen; Merck Sharp & Dohme; Viralytics (Inst). Research Funding - AstraZeneca; Genelux Oncolytics Biotech, Viralytics Travel - Boehringer Ingelheim, Viralytics. C. Ralph: Travel, Accommodations, Expenses – Viralytics. A. Melcher: Research Funding - Oncolytics Biotech, Viralytics Limited Travel, Accommodations, Expenses – Viralytics. E. Schmidt, D.R. Kaufman: Employment: Merck & Co. M. Grose, R. Karpathy, D. Shafren: Viralytics stock and employment.