BVAC-C Vaccine Therapy Plus Durvalumab Elicits Responses in Recurrent HPV+ Cervical Cancer

Durvalumab (Imfinzi) plus BVAC-C demonstrated durable antitumor activity in patients with human papillomavirus (HPV)–positive cervical cancer who had progressed on first-line platinum-based chemotherapy, according to findings from the single-arm phase 2 DURBAC trial (NCT04800978), which were presented at the 2025 SGO Annual Meeting on Women’s Cancer.1

Of the 29 efficacy-evaluable patients who received at least 1 dose of BVAC-C or durvalumab, the 6-month progression-free survival (PFS) rate was 52% (95% CI, 36%-74%), and the median PFS was 8.7 months. The overall response rate (ORR) was 38% (95% CI, 20%-56%) and included best responses of complete response (CR; 17%), partial response (PR; 21%), stable disease (SD; 24%), and progressive disease (PD; 38%). The median duration of response (DOR) was 20 months (range, 9-not available).

The Evolution of Recurrent Cervical Cancer Therapy

Treatment strategies for patients with recurrent cervical cancer have evolved over the past several years. In the frontline setting, the phase 3 GOG 204 trial showed that cisplatin plus paclitaxel led to a median overall survival (OS) of 12.0 months and an ORR of 29.1%. The phase 3 GOG-240 trial (NCT00803062) showed that nonplatinum combination chemotherapy plus bevacizumab (Avastin) resulted in a median OS of 17.0 months and an ORR of 48.0%. The phase 3 KEYNOTE-826 trial (NCT03635567) showed that treatment with chemotherapy plus pembrolizumab (Keytruda) with or without bevacizumab led to a median OS of 24.4 months; among patients with PD-L1 expression of at least 1, the ORR was 68.1%.

In the second-line setting, the phase 3 EMPOWER-Cervical 1 trial (NCT03257267) showed that treatment with cemiplimab (Libtayo) led to a median OS of 12.0 months with a median PFS of 2.8 months. The ORR among patients with PD-L1 expression of at least 1 was 18.0%. Additionally, the phase 3 innovaTV 301 trial (NCT04697628) showed that treatment with tisotumab vedotin-tftv (Tivdak) resulted in a median OS of 11.5 months, a median PFS of 4.2 months, and an ORR of 17.8%.

BVAC-C is a therapeutic vaccine that activates innate anticancer immunity through natural killer (NK) and NKT cells; it also activates adaptive anticancer immunity through CD4-positive and CD8-positive T cells. A phase 1/2a trial examined BVAC-C monotherapy in patients with HPV16- or HPV18-positive cervical carcinoma who had progressed on frontline platinum-based chemotherapy and demonstrated an ORR of 19.2% (95% CI, 4.1%-34.4%), a disease control rate (DCR) of 53.8% (95% CI, 34.7%-73.0%), a median DOR of 7.5 months (95% CI, 7.1-not reported), a median PFS of 5.8 months (95% CI, 4.2-10.3), and a median OS of 17.7 months (95% CI, 12.0-not reported).2

Furthermore, anticancer DNA and peptide vaccines in combination with immune checkpoint inhibitors (ICIs) have demonstrated improved clinical activity compared with BVAC-C monotherapy.1 Pembrolizumab plus GX-188E elicited an ORR of 31%. Atezolizumab (Tecentriq) plus VB10.16 generated an ORR of 21%. Treatment with durvalumab plus MEDI0457 led to a 0% ORR but a clinically meaningful DCR. Cemiplimab plus ISA101b has also shown activity.

DURBAC Trial Design

The DURBAC trial aimed to address the need for improved second-line treatment options based on the demonstrated efficacy of anticancer vaccines plus ICIs in patients with recurrent cervical cancer. This trial enrolled patients older than 20 years of age with recurrent or metastatic cervical cancer who had progressed during or had disease recurrence after prior frontline platinum-based chemotherapy with or without bevacizumab. Patients needed to have HPV16- or HPV18-positive disease, at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy longer than 3 months. Patients were excluded if they had neuroendocrine or small cell carcinoma disease histology, peritoneal carcinomatosis, and/or a history of serious allergic reaction to the study drugs.

Part A—the safety lead-in phase—used a 3+3 dose-escalation design and treated patients with durvalumab plus BVAC-C at 1 of 2 doses: 1 x 107 cells per dose (dose 1) or 5 x 107 cells per dose (dose 2). Patients received combination therapy for 4 cycles followed by durvalumab monotherapy for approximately 21 cycles. After the safety review for part A, part B treated patients with BVAC-C monotherapy at the chosen dose to explore its safety and efficacy.

The primary end point was 6-month PFS rate. Secondary end points included 6-month ORR, 6- and 12-month DCRs, 12-month PFS rate, 12-month OS rate, and safety.

A total of 40 patients were enrolled, 6 of whom did not pass screening and 4 of whom withdrew consent. Thirty patients received at least 1 dose of BVAC-C or durvalumab, 19 of whom discontinued treatment due to disease progression (n = 15), adverse effects (AEs; n = 1), or withdrawal of consent (n = 3); and 3 of whom completed treatment. Treatment was ongoing in 8 patients at data cutoff.

Subgroup-Specific Efficacy Findings

Among the 30 safety-evaluable patients, 60% had squamous cell carcinoma histology, and 40% had adenocarcinoma/adenosquamous carcinoma histology. Most patients had a treatment-free interval of longer than 6 months (56.7%). Target lesions were located in the lung (55%), lymph nodes (55%), and pelvis (35%). In total, 73.3% and 33.3% of patients had HPV16- and HPV18-positive disease, respectively. Most patients (73.3%) had PD-L1–positive disease.

Response rates were higher in patients with PD-L1–negative disease. Of the patients with PD-L1–negative disease, the respective CR, PR, SD, and PD rates were 25%, 50%, 0%, and 25%. These respective rates in patients with PD-L1–positive disease were 18%, 9%, 36%, and 36%.

Higher response rates were also observed among patients with squamous cell carcinoma vs adenocarcinoma/adenosquamous carcinoma histology. Among patients with squamous cell carcinoma histology, the respective CR, PR, SD, and PD rates were 22%, 28%, 11%, and 39%. These respective rates in patients with adenocarcinoma/adenosquamous carcinoma histology were 9%, 9%, 46%, and 36%.

Among patients with a treatment-free interval of longer than 6 months, the respective CR, PR, SD, and PD rates were 29%, 24%, 29%, and 18%. These respective rates in patients with a treatment-free interval of 6 months or shorter were 0%, 17%, 17%, and 67%. Patients with a treatment-free interval of longer than 6 months also had improved PFS and OS outcomes vs those with a treatment-free interval of 6 months or shorter.

Safety and Immunological Response Findings

The most common AEs included fever (grade 1, 63.3%; grade 2, 13.3%; grade 3, 0%), thyroid dysfunction (26.7%; 0%; 0%), rash (16.7%; 0%; 3.3%), headache (16.7%; 3.3%; 0%), fatigue (16.7%; 0%; 0%), constipation (13.3%; 6.6%; 3.3%), dyspepsia (10.0%; 3.3%; 0%), diarrhea (6.7%; 6.6%; 0%), cough (6.7%; 3.3%; 0%), back pain (6.7%; 0%; 3.3%), chest discomfort (6.6%; 0%; 3.3%), dizziness (6.6%; 0%; 0%), dyspnea (3.3%; 3.3%; 0%), insomnia (3.3%; 3.3%; 0%), vomiting (3.3%; 0%; 0%), ileus (3.3%; 0%; 0%), urticaria (3.3%; 0%; 0%), arthralgia (3.3%; 0%; 0%), myalgia (3.3%; 0%; 0%), conjunctivitis (3.3%; 0%; 0%), cytokine release syndrome (3.3%; 0%; 0%), herpes zoster (3.3%; 0%; 0%), anorexia (0%; 3.3%; 0%), elevated cardiac marker levels (0%; 0%; 3.3%), and increased blood creatinine levels (0%; 0%; 3.3%).

Notably, levels of the serum cytokines IFN-γ and TNF-α generally decreased from baseline levels during the first 4 cycles of therapy.

“BVAC-C has a manageable safety profile and can be produced within 1 day, making it a significant option for second-line treatment,” the study authors concluded in the presentation.

Disclosures: Choi had no disclosures to report.

References

1. Choi CH, Lee JW, Kim TJ, et al. An open label, single arm phase II, multicenter trial of durvalumab and BVAC-C, in patients with HPV 16 or 18 positive cervical cancer failure to first-line platinum-based chemotherapy (DURBAC, NCT04800978). Presented at: 2025 SGO Annual Meeting on Women’s Cancer. March 14-17, 2025; Seattle, WA. Abstract 938773.
2. Choi CH, Lee JW, Bae DS, et al. Efficacy and safety of BVAC-C in HPV type 16- or 18-positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study. Front Immunol. Published online March 28, 2024. doi:10.3389/fimmu.2024.1371353