In a single-center phase I/II trial reported in JAMA Oncology, Floudas et al found that the combination of the human papillomavirus (HPV) type 16 therapeutic vaccine PDS0101, the tumor-targeting interleukin-12 antibody-drug conjugate PDS01ADC, and the bifunctional PD-L1/TGF-β inhibitor bintrafusp alfa was active in patients with advanced or metastatic HPV-associated cancers.
Study Details
In the trial, 50 patients enrolled at the Center for Cancer Research of the National Cancer Institute between June 2020 and July 2022 received the following regimen: PDS0101 at 1 mL subcutaneously (SC) every 4 weeks for six doses and then every 12 weeks for two additional doses; PDS01ADC at 16.8 μg/kg SC every 4 weeks or 8 μg/kg SC every 2 weeks; and bintrafusp alfa at 1,200 mg intravenously every 2 weeks. Among the 50 patients, 14 were immune checkpoint blockade (ICB)-naive, and 36 were ICB-resistant.
Key Findings
The median follow-up was 37.7 months (interquartile range = 30.6–42.0 months).
Among 14 ICB-naive patients, objective responses were observed in 5 patients (35.7%, 95% confidence interval [CI] = 12.8%–64.9%); median overall survival was 42.4 months (95% CI, 8.3 months to not estimable). Among 36 ICB-resistant patients, objective responses were observed in 6 patients (16.7%, 95% CI = 6.4%–32.8%); median overall survival was 15.8 months (95% CI = 9.0–21.3 months).
Among eight patients with HPV16-positive tumors in the ICB-naive group, objective responses were observed in 5 patients (62.5%, 95% CI = 24.5%–91.5%), and median overall survival was not reached. Among 29 patients with HPV16-positive tumors in the ICB-resistant group, objective response was observed in 6 patients (20.7%, 95% CI = 8.0%–39.7%), and median overall survival was 17.0 months (95% CI = 10.4–22.8 months).
Grade ≥ 3 treatment-related adverse events occurred in 26 of 50 patients (52%), most commonly anemia (26%), total mucosal bleeding (18%), and hematuria (10%). No treatment-related deaths were observed.
The investigators concluded: “In this trial, the combination of PDS0101, PDS01ADC, and bintrafusp alfa showed an acceptable safety profile and promising antitumor activity and improved [overall survival] in patients with [HPV16-positive] cancers, in both ICB-naive and ICB-resistant patients, warranting further evaluation of the combination of PDS0101 and PDS01ADC with simultaneous PD-L1/TGF-β inhibition in these populations.”
Charalampos S. Floudas, MD, DMSc, MS, of the Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
