Expanded interim data from a phase II clinical trial investigating PDS0101-based triple combination therapy in advanced human papillomavirus (HPV)-positive cancers were recently announced. The triple combination of PDS0101—a novel T-cell HPV-specific immunotherapy—with the tumor-targeting IL-12 fusion protein M9241 (formerly known as NHS-IL12), and bintrafusp alfa, a bifunctional fusion protein targeting two independent immunosuppressive pathways (PD-L1 and TGF-β), is being studied in checkpoint inhibitor–naive and checkpoint inhibitor–refractory patients with advanced HPV-positive anal, cervical, head and neck, vaginal, and vulvar cancers.
The triple-combination phase II trial (ClinicalTrials.gov identifier: NCT04287868) is being conducted at the Center for Cancer Research at the National Cancer Institute.
All patients in the study had experienced disease progression on prior treatment with chemotherapy, and 90% had progressed after radiation treatment. The interim efficacy data (n = 50) involved 37 HPV16-positive evaluable patients, including 29 patients who were checkpoint inhibitor–refractory.
Highlights of the expanded interim data are as follows:
- The median overall survival was 21 months in 29 checkpoint inhibitor–refractory patients who received the triple combination; the reported historical median overall survival in patients with checkpoint inhibitor–refractory disease is 3 to 4 months.
- In checkpoint inhibitor–naive patients, 75% remain alive at a median follow-up of 27 months; as a result, median overall survival has not yet been reached. Historically, the median overall survival for similar patients with platinum-experienced, checkpoint inhibitor–naive disease is 7 to 11 months.
- The objective response rate in checkpoint inhibitor–refractory patients who received the optimal dose of the triple combination was 63% (5 of 8 patients). In current approaches, the objective response rate is reported to be less than 10%.
- The objective response rate in checkpoint inhibitor–naive patients with the triple combination was 88%. In current approaches, the objective response rate is reported to be less than 25% with U.S. Food and Drug Administration–approved checkpoint inhibitors in HPV-associated cancers.
- 48% (24 of 50) of patients experienced grade 3 treatment-related adverse events, and 4% (2 of 50) of patients experienced grade 4 events, compared with approximately 70% of patients receiving the combination of checkpoint inhibitors and chemotherapy reporting grade 3 and higher treatment-related adverse events.
