A Phase I Dose-Escalation Trial of BN-CV301, a Recombinant Poxviral Vaccine Targeting MUC1 and CEA with Costimulatory Molecules

Purpose: BN-CV301 is a poxviral-based vaccine comprised of recombinant (rec.) modified vaccinia Ankara (MVA-BN-CV301; prime) and rec. fowlpox (FPV-CV301; boost). Like its predecessor PANVAC, BN-CV301 contains transgenes encoding tumor-associated antigens MUC1 and CEA as well as costimulatory molecules (B7.1, ICAM-1, and LFA-3). PANVAC was reengineered to make it safer and more antigenic. Patients and Methods: This open-label, 3+3 design, dose-escalation trial evaluated three dose levels (DL) of MVA-BN-CV301: one, two, or four subcutaneous injections of 4 x 10(8) infectious units (Inf.U)/0.5 mL on weeks 0 and 4. All patients received FPV-CV301 subcutaneously at 1 x 10(9) Inf.U/0.5 mL every 2 weeks for 4 doses, then every 4 weeks. Clinical and immune responses were evaluated. Results: There were no dose-limiting toxicities. Twelve patients enrolled on trial [dose level (DL) 1 = 3, DL2 = 3, DL3 = 6). Most side effects were seen with the prime doses and lessened with subsequent boosters. All treatment-related adverse events were temporary, self-limiting, grade 1/2, and included injection-site reactions and flu-like symptoms. Antigen-specific T cells to MUC1 and CEA, as well as to a cascade antigen, brachyury, were generated in most patients. Single-agent BN-CV301 produced a confirmed partial response (PR) in 1 patient and prolonged stable disease (SD) in multiple patients, most notably in KRAS-mutant gastrointestinal tumors. Furthermore, 2 patients with KRAS-mutant colorectal cancer had prolonged SD when treated with an anti-PD-L1 antibody following BN-CV301. Conclusions: The BN-CV301 vaccine can be safely administered to patients with advanced cancer. Further studies of the vaccine in combination with other agents are planned.