CV301 comprises recombinant poxviruses, Modified Vaccinia Ankara (MVA) and Fowlpox (FPV), encoding CEA, MUC-1, and co-stimulatory Molecules (TRICOM) ICAM-1, LFA-3, and B7-1. MVA-BN-CV301 is used for priming and FPV-CV301 is used for boosting.
A Phase 2, single-arm trial was designed to evaluate CV301 plus atezolizumab as first-line treatment for cisplatin-ineligible advanced urothelial carcinoma (aUC) (Cohort 1) or progressing after platinum chemotherapy (Cohort 2). MVA-CV301 was given subcutaneously (SC) on Days 1 and 22 and FPV-CV301 SC from day 43 every 21 days for 4 doses, then tapered gradually over up to 2 years. Atezolizumab 1200 mg IV was given every 21 days. The primary endpoint was objective response rate (ORR). Overall, 43 evaluable patients received therapy: 19 in Cohort 1; 24 in Cohort 2; nine experienced ≥ Grade 3 therapy-related adverse events. In Cohort 1, one had partial response (PR) (ORR 5.3%, 90% CI 0.3, 22.6). In Cohort 2, 1 complete response and 1 PR were noted (ORR 8.3%, 90% CI 1.5, 24.0). The trial was halted for futility. Patients exhibiting benefit demonstrated T-cell response to CEA and MUC-1. The trial illustrates the challenges in the development of vaccines, which should be guided by robust preclinical data.
Cancer immunology, immunotherapy : CII. 2022 Aug 23 [Epub ahead of print]
Guru P Sonpavde, Benjamin Louis Maughan, Bradley Alexander McGregor, Xiao X Wei, Kerry L Kilbridge, Richard J Lee, Evan Y Yu, Michael Thomas Schweizer, Robert B Montgomery, Heather H Cheng, Andrew Caleb Hsieh, Rohit Jain, Jaspreet S Grewal, Cesar Pico-Navarro, Zarina Gafoor, Teresa Perschy, Petros Grivas
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, D-924, Boston, MA, 02215, USA. ., University of Utah Cancer Center, Salt Lake City, UT, USA., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, D-924, Boston, MA, 02215, USA., Massachusetts General Hospital, Boston, MA, USA., Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA., H. Lee Moffitt Cancer Center, Tampa, FL, USA., Norton Cancer Institute, Louisville, KY, USA., Bavarian Nordic, Inc., Morrisville, NC, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35998004