A Potential Second-Line Treatment for Cervical Cancer
Combining BVAC-C and durvalumab in recurrent or metastatic cervical cancer.
Although pembrolizumab has become a standard first-line therapy for patients with recurrent or metastatic cervical cancer, second-line options have proven more difficult to come by.
A combination of BVAC-C, an HPV-specific therapeutic vaccine, combined with durvalumab, a PD-L1 inhibitor, is showing promise in addressing a need for immune checkpoint inhibitors (ICIs) in second-line or later settings for recurrent cervical cancer patients.
In “Combination of BVAC-C and durvalumab in recurrent or metastatic cervical cancer,” the prospective, open-label, single-arm phase 2 trial has evaluated the safety and efficacy of BVAC-C and durvalumab in patients with HBV-16-/18-positive recurrent/metastatic cervical cancer (rmCC) refractory to — or relapsed after — platinum-based chemotherapy.
“Our findings highlight the potential for combining a therapeutic HPV vaccine with immune checkpoint inhibition to enhance antitumor immune responses in recurrent/metastatic cervical cancer,” said lead investigator Chel Hun Choi, MD, PhD, professor of gynecologic oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, in Seoul, South Korea. “The study suggests that this strategy could improve response rates and disease control, offering a novel treatment approach for patients.”
The study consisted of a safety lead-in phase and a non-randomized, single-arm efficacy phase. The primary endpoint was the six-month progression-free survival (PFS) rate. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), safety, and exploratory immunological analyses.
A total of 30 patients were treated as part of the study, and at 24 weeks, the ORR was 37.9%, with a DCR of 62.1%. Patients with a treatment-free interval longer than six months demonstrated superior outcomes with an ORR of 52.9%. Median PFS was 8.7 months, with a six-month PFS rate of 51.7%. Median overall survival was not reached at a median follow-up of 9.8 months. Dr. Choi said updated immunological data are currently being evaluated to refine predictive biomarkers of response and will be incorporated into future analyses.
Another key finding of the trial, Dr. Choi explained, is the potential predictive value of treatment-free intervals (TFI) and histologic subtype in determining the response to the treatment.
“Patients with longer TFIs and squamous cell carcinoma exhibited better outcomes, suggesting these factors should be considered in future study designs,” he said.
Dr. Choi said the overall findings of the study could pave the way for a new treatment paradigm in cervical cancer by addressing resistance to single-agent checkpoint inhibitors.
“By targeting HPV oncoproteins and activating tumor-specific T-cell responses, this approach may lead to more durable responses,” Dr. Choi said. “If validated in larger trials, this strategy could expand the role of immunotherapy in cervical cancer and improve survival for patients with advanced disease.”
But before that can happen, the next steps include expanding clinical evaluation in a larger patient population and conducting randomized trials to compare BVAC-C plus durvalumab against current standard therapies, Dr. Choi said.
“Additionally, biomarker-driven analyses will be crucial in identifying patient subgroups most likely to benefit,” he added. “Future studies may also explore combinations with other immunomodulators or targeted therapies to further enhance treatment efficacy.”
