On December 28, 2022 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing a growing pipeline of targeted immunotherapies for cancer and infectious disease, reported expanded interim data in a Phase 2 clinical trial investigating the PDS0101-based triple combination therapy in advanced human papillomavirus (HPV)-positive cancers (Press release, PDS Biotechnology, DEC 28, 2022, View Source [SID1234625644]). The triple combination of PDS0101 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 CPI-naïve and CPI-refractory patients with advanced HPV-positive anal, cervical, head and neck, vaginal, and vulvar cancers.

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The triple combination Phase 2 trial (NCT04287868) is being conducted at the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), one of the Institutes of the National Institutes of Health.

All patients in the study had failed prior treatment with chemotherapy and 90% had failed radiation treatment. The interim efficacy data (n=50) involves 37 HPV16-positive evaluable patients, including 29 patients who have, in addition, failed treatment with CPIs (CPI refractory). Highlights of the expanded interim data are as follows and are consistent with the results presented at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2022 and prior interim data announced in October:

Median OS is 21 months in 29 checkpoint inhibitor refractory patients who received the triple combination. The reported historical median OS in patients with CPI refractory disease is 3-4 months.

In CPI naïve subjects, 75% remain alive at a median follow-up of 27 months. As a result, median OS has not yet been reached. Historically median OS for similar patients with platinum experienced CPI naïve disease is 7-11 months.

Objective response rate (ORR) in CPI refractory patients who received the optimal dose of the triple combination is 63% (5/8). In current approaches ORR is reported to be less than 10%.

ORR in CPI naïve patients with the triple combination is 88%. In current approaches ORR is reported to be less than 25% with FDA-approved CPIs in HPV-associated cancers.

Safety data have not changed since October’s update. 48% (24/50) of patients experienced Grade 3 (moderate) treatment-related adverse events (AEs), and 4% (2/50) patients experienced Grade 4 (severe) AEs, compared with approximately 70% of patients receiving the combination of CPIs and chemotherapy reporting Grade 3 and higher treatment-related AEs.

"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," stated Dr. Frank Bedu-Addo, President and Chief Executive Officer of PDS Biotech. "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."

Both M9241 and bintrafusp alfa are owned by Merck KGaA, Darmstadt, Germany, and its affiliates.