PDS0101-Based Triplet Produces Prolonged OS in Refractory HPV+ Cancers

Treatment with PDS0101 plus the tumor-targeting IL-12 fusion protein M9241 and bintrafusp alfa elicited encouraging overall survival data in patients with checkpoint inhibitor–naïve and –refractory advanced human papillomavirus–positive anal, cervical, head and neck, vaginal, and vulvar cancer.

Frank Bedu-Addo, PhD

Frank Bedu-Addo, PhD

Treatment with PDS0101 plus the tumor-targeting interleukin-12 (IL-12) fusion protein M9241 (NHS-IL12) and bintrafusp alfa elicited encouraging overall survival (OS) data in patients with checkpoint inhibitor (CPI)–naïve and CPI-refractory advanced human papillomavirus (HPV)–positive anal, cervical, head and neck, vaginal, and vulvar cancer, according to updated interim findings from a phase 2 trial (NCT04287868).1

The results showed that treatment with the triplet therapy led to a median OS of 21 months in 29 CPI-refractory patients. In CPI-naïve patients, the median OS was not reached, with 75% of patients still alive at a median follow-up of 27 months.

Findings from the expanded interim data set were consistent with the results presented at the 2022 ASCO Annual Meeting and prior interim data announced in October.

“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 of PDS Biotech, said in a 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.”

Patients with CPI-refractory disease have a poor survival ranging from 3 to 4 months and those with platinum-pretreated, CPI-naïve disease have an OS between 7 and 11 months. Response rates are also poor with current approaches ranging from less than 10% in CPI-refractory patients and less than 25% in CPI-naïve patients.

Preclinical studies have shown that the addition of PDS0101, a therapeutic vaccine targeting HPV 16 E6/E7 to M9241, a tumor-targeting IL-12 immunocytokine, and bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, led to maximum T-cell infiltration and tumor reduction compared with any 1 or 2 of these agents alone.2 Additionally, prior clinical data suggests that the triplet therapy is preferentially active in HPV 16–positive disease.

In the study, patients received 1200 mg of intravenous bintrafusp alfa at every 2 weeks, 16.8 μg/kg of subcutaneous M9241 every 4 weeks or 8 μg/kg every 2 weeks, and two 0.5-ml injections of every 4 weeks. Dose reductions or skipped doses for toxicities of bintrafusp alfa and M9241 were allowed.

All patients in the study were refractory to chemotherapy and 90% had failed radiation treatment. The interim efficacy data (n = 50) consisted of 37 evaluable patients with HPV16-positive disease, including 29 patients who had also failed prior treatment with CPIs.

Additional results indicated that the objective response rate (ORR) in CPI-refractory patients and CPI-naïve patients was 63% (n = 5/8) and 88%, respectively.

Regarding safety, data remained unchanged since October’s update and favored the use of CPIs plus chemotherapy, in which approximately 70% of patients experience grade 3 or higher treatment-related adverse effects (TRAEs). Grade 3 TRAEs occurred in 48% (n = 24/50) of patients, and grade 4 AEs occurred in 4% (n = 2/50) of patients.


  1. 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, 2022. https://bit.ly/3Q89I25
  2. Strauss J, Floudas CS, Pastor DM, et al. Phase II evaluation of the combination of PDS0101, M9241, and bintrafusp alfa in patients with HPV 16+ malignancies. J Clin Oncol. 2022;40(suppl 16):2518. doi:10.1200/JCO.2022.40.16_suppl.2518
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