An open label, single arm phase II, multicenter trial of durvalumab and BVAC-C, in patients with HPV 16- or 18-positive cervical cancer and failure of first-line platinum-based chemotherapy (DURBAC).

5513 Background: In the phase I/IIa study of HPV positive recurrent cervical carcinoma, BVAC-C, a pioneering B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant E6/E7 gene of HPV type 16/18, demonstrated favorable tolerability. The ongoing phase 2 clinical trial investigates the potential synergistic effects of combining BVAC-C with durvalumab (MEDI4736), an anti-PD-L1 therapy, to enhance anti-tumor immune responses. Methods: The trial comprises two parts. Part A, utilizing a 3+3 dose-escalation design, assesses BVAC-C combined with 1500 mg durvalumab to establish the maximum tolerated dose (MTD) and recommended dose for Part B. Part B, with an expansion phase involving up to 25 patients, focuses on safety and clinical efficacy, measured by the 6-month progression-free survival (PFS) rate. Part A enrollment commenced in September 2021 across six Korean centers, with 9 participants enrolled and MTD determined by November 2022. 25 patients were enrolled in Part B enrollment was completed with 25 patients by December 2023. Tumor response evaluation follows RECIST 1.1 criteria and iRECIST. The essential eligibility criteria comprise histologically confirmed cervical carcinoma with HPV 16/18 positivity, recurrence following or resistance to a solitary prior first-line platinum-based chemotherapy ± bevacizumab, lack of prior exposure to immune-oncology (IO) drugs, and the presence of measurable disease according to RECIST v1.1. Results: Among 29 patients available for this interim analysis, 6-month PFS-rate was 51% (95% CI 33 – 77). The objective response rate (ORR) was 29.2% (7/24), with 2 complete responses. The disease control rate (DCR) was 66.7% (16/24). With a median follow up of 7 months, the median duration of response (DOR) and PFS were not reached. All evaluated patients exhibited inflammatory cytokine responses (IFN-γ or TNF-α) and robust E6/E7-specific T cell responses following BVAC-C vaccinations. Notably, immune responses correlated with clinical outcomes. The most common treatment-emergent adverse events (TEAEs) were pyrexia and myalgia, mostly grade 1 and manageable. Conclusions: The combination of BVAC-C and durvalumab demonstrates promise as a second-line treatment option with a manageable safety profile for patients with recurrent HPV 16/18 positive cervical cancer. The survival data is scheduled to receive an update during the upcoming ASCO meeting. Further studies are warranted to identify potential biomarkers of treatment response. Clinical trial information: NCT04800978 .