학술논문
Phase II trial of CV301 vaccine combined with atezolizumab in advanced urothelial carcinoma.
Document Type
Article
Author
Sonpavde, Guru P.; Maughan, Benjamin Louis; McGregor, Bradley Alexander; Wei, Xiao X.; Kilbridge, Kerry L.; Lee, Richard J.; Yu, Evan Y.; Schweizer, Michael Thomas; Montgomery, Robert B.; Cheng, Heather H.; Hsieh, Andrew Caleb; Jain, Rohit; Grewal, Jaspreet S.; Pico-Navarro, Cesar; Gafoor, Zarina; Perschy, Teresa; Grivas, Petros
Source
Subject
*TRANSITIONAL cell carcinoma
*VACCINE trials
*ATEZOLIZUMAB
*VACCINE development
*VACCINIA
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Language
ISSN
0340-7004
Abstract
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. [ABSTRACT FROM AUTHOR]