PDS0101-Based Triplet Improves Overall Survival in HPV-Positive Cancers


The combination of PDS0101, M9241, and bintrafusp alfa elicited a promising median overall survival in patients with checkpoint inhibitor refractory advanced human papillomavirus-positive cancers.

Expanded interim data from a phase 2 trial (NCT04287868) examining a PDS0101-based triple combination therapy led to a median overall survival of (OS) 21 months in 29 patients with checkpoint inhibitor (CPI) refractory advanced human papillomavirus (HPV)-positive cancers, according to PDS Biotechnology Corporation.1

The study evaluated the triple combination of PDS0101 plus the tumor-targeting IL-12 fusion protein M9241 (formerly known as NHS-IL12), and bintrafusp alfa (M7824), a bifunctional fusion protein which targets the PD-L1 and TGF-β pathways.

A total of 50 patients were enrolled at the time of this interim efficacy data, including 37 with HPV16-positive evaluable disease and 29 patients who have also failed treatment with CPIs. Those enrolled were patients with CPI-naïve and CPI-refractory advanced HPV-positive anal, cervical, head and neck, vaginal, and vulvar cancers.

“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,” said Frank Bedu-Addo, MD, president, and chief executive officer of PDS Biotechnology Corporation, in the press release. “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.”

Within the study, patients were administered the PDS0101-based triplet combination with the goal of learning if multiple immunotherapy drugs combined can shrink tumors in patients with HPV-associated cancers.2

Enrollment in the trial was open to patients who had failed prior treatment with chemotherapy. Patients must be aged 18 years and older with locally advanced or metastatic HPV associated cancer, have measurable disease per RECIST 1.1., an ECOG performance status of 0-2, and have adequate hematologic, renal, and hepatic function. Among those enrolled, 90% of patients had failed radiation treatment.

The primary end point of the trial was to evaluate the objective response rate (ORR) with secondary end points including safety, progression-free survival, OS, adverse events (AEs), and the safety of the reduced dose level in specific patients with cervical cancer

According to data presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, the median OS was 21 months in the 29 CPI refractory patients given the triple combination. This shows a significant improvement compared with the historical median OS in this patient population at 3-4 months.

At a median follow-up of 27 months, 75% of CPI naïve patients remained alive. The median OS has not yet been reached but historically, the median OS for similar patients is 7-11 months.

For CPI refractory patients who were given the optimal dose of the combination, the ORR was 63% in 5 of the 8 patients. Previous data has reported the ORR for this patient population to be less than 10%. Then for patients with CPI-naïve disease, their ORR with the triple combination was 88% compared with current approaches which have demonstrated their ORR to be less than 25%.

Regarding safety, 48% (n = 24) of all patients experienced grade 3 treatment-related AEs. Four percent (n = 2) of patients had severe grade 4 AEs. Comparatively, approximately 70% of patients receiving the combination of CPIs and chemotherapy have reported having grade 3 or higher treatment-related AEs.

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 4, 2023. https://bit.ly/3Gds1OF
Combination immunotherapy in subjects with advanced HPV associated malignancies. ClinicalTrials.gov. Updated December 20, 2022. Accessed January 4, 2023. https://clinicaltrials.gov/ct2/show/NCT04287868

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