Phase II Trial of CV301 Vaccine Combined with Atezolizumab in Advanced Urothelial Carcinoma - Beyond the Abstract

The combination of atezolizumab with CV301, a second-generation off-the-shelf poxvirus vaccine containing transgenes encoding tumor-associated antigens commonly expressed in urothelial carcinoma, MUC1 and CEA, and co-stimulatory molecules B7.1, ICAM-1, and LFA-3, did not demonstrate sufficient efficacy in advanced urothelial carcinoma (aUC). Two cohorts of patients were evaluated in a phase II trial: 1) first-line therapy in cisplatin-ineligible patients or in 2) the platinum-refractory setting.

Among 43 evaluable patients overall including both cohorts, objective response was observed in 3 (7%) and SD (as best response) in 8 (19%) patients. The toxicity profile was acceptable with no treatment related mortality and low rates of discontinuations due to toxicities. Given these disappointing efficacy data, the trial was halted at the interim analysis, notwithstanding modifications of CEA and MUC1 to induce a stronger immune response with enhanced HLA binding and T-cell recognition, no significant increase in CEA- and MUC-1-specific T cells was observed. While the reasons for these poor outcomes are unclear, the patients were elderly, had advanced and aggressive disease, and were not selected for high expression of CEA or MUC1.

While ‘off-the-shelf’ poxvirus vaccines are more user-friendly, practical, safe, and likely affordable, their efficacy remains in question. The development of vaccines may warrant a more optimal selection of patients with earlier stage disease to allow longer duration of safe therapy that may yield a more robust immune response. Additionally, the activity may benefit certain molecular subgroups. Finally, optimal partners for combination therapy incorporating vaccines require investigation.

Written by: Guru P. Sonpavde, MD, Genitourinary Oncology Director, Christopher K. Glanz Chair for Bladder Cancer Research, Assistant Director Phase I Clinical Research Unit, AdventHealth Cancer Institute

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