PDS0101-Based Triplet Regimen Demonstrates Long-Lasting Benefit in Difficult-to-Treat, HPV+ Cancers

A triplet, PDS0101-based combination regimen enhanced survival across several types of HPV-positive cancer, according to interim data from a phase 2 trial.

A combination of PDS0101, M9241—a tumor-targeting IL-12 fusion protein—and bintrafusp α—a bifunctional fusion protein targeting the independent immunosuppressive pathways PD-L1 and TGF-β—prolonged overall survival (OS) in patients with advanced human papillomavirus 16 (HPV16)–positive cancers, according to a press release from PDS Biotechnology on interim efficacy data from a phase 2 trial (NCT04287868).

Median overall survival (OS) was 21 months among patients refractory to a prior checkpoint inhibitor (CPI; n = 29). Importantly, the reported historical median OS ranges from 3 to 4 months in patients with CPI-refractory disease. The objective response rate (ORR) was 63% among patients refractory to a CPI who received the optimal dose of the regimen (n = 8).

Additionally, the ORR was 88% among patients who were CPI therapy naïve. Investigators reported that 75% this population remained alive at a median follow-up of 27 months. Median OS has not yet been reached; the reported historical median OS for this population is approximately 7 to 11 months.

“The expanded data continue to demonstrate the durability and tolerability of the PDS0101-based triple combination therapy in advanced HPV-positive cancers, an extremely challenging population of refractory and previously untreatable HPV-positive patients,” Frank Bedu-Addo, PhD, president and chief executive officer at PDS Biotech, said in the press release.

The study included patients with anal, cervical, head and neck, vaginal, and vulvar cancers. All enrolled patients experienced progressed on treatment with chemotherapy and most (90%) progressed following radiation therapy. Investigators derived this interim efficacy data from a population of 50 patients, including 37 evaluable patients with HPV16-positive disease.

Patients need to have received at least 1 prior systemic chemotherapy to be included in the study. They must also have undergone treatment with a CPI if an FDA-approved option was available unless they were ineligible or unwilling after appropriate counseling. An ECOG performance status of 2 or lower, adequate hematologic function, and adequate renal and hepatic function at screening were also required.

Exclusion criteria included known brain or central nervous system (CNS) metastases, as well as seizures requiring anticonvulsant treatment or clinically significant cerebrovascular accidents in the 3 months prior to the start of treatment. Patients were also excluded if they had a non-HPV associated second malignancy within 3 years of enrollment; the only exceptions were adequately treated, localized malignancies, and malignancies requiring no active systemic treatment.

“We are pleased to see the continued consistency in the data with each update and we look forward to meeting with the FDA to discuss the registrational pathway,” Bedu-Addo added.

PDS0101 is also under assessment in the phase 2 VERSATILE002 study (NCT04260126) in combination with pembrolizumab (Keytruda) as well as the phase 2A IMMUNOCERV trial (NCT04580771) in patients with locally advanced cervical cancer.


PDS Biotech reports median overall survival (OS) of 21 months in advanced, refractory cancer patients having few remaining treatment options and with reported historical survival of 3-4 months. News Release. PDS Biotechnology Corporation. December 28, 2022. Accessed January 3, 2023. https://bit.ly/3GCvg3E