PDS0101-Based Triplet Provides Survival Benefit in HPV16+ Cancers


The combination of PDS0101, PDS0301 (formerly M-9241), and bintrafusp alfa, an investigational immune checkpoint inhibitor (ICI) extended survival in patients with advanced human papillomavirus (HPV)16–positive cancers, according to final data from a phase 2 trial (NCT04287868) led by the National Cancer Institute.1

Data indicated that 75% of the group of patients who had not responded to standard-of-care treatments but had not been exposed to an ICI (n = 8) were still alive at 36 months. The median overall survival (OS) in this ICI-naive group was not yet reached (NR).

In the group of patients who had not responded to several prior treatments, including ICI therapy, the median OS was approximately 20 months, and the 12-month OS rate was 72%. In this group, when PDS0101 was paired with PDS0301 and high doses of ICI (n = 8), the overall response rate (ORR) was 63%. When PDS0101 was combined with low doses of ICI and/or PDS0301 (n = 21), the ORR was much lower, at 5%.

“We are encouraged by the survival rates for both ICI-naive and ICI-resistant patients with HPV16-positive cancers who were treated with the triple combination therapy,” Frank Bedu-Addo, PhD, chief executive officer of PDS Biotechnology Corporation, stated in a press release.

The phase 2 trial enrolled patients with cytologically or histologically confirmed locally advanced or metastatic HPV-associated malignancies, which included cervical cancers; cyclin-dependent kinase inhibitor 2A oropharyngeal cancers; anal cancers; vulvar, vaginal, penile, and squamous cell rectal cancers; and other solid tumors such as lung or esophageal cancers.2

Patients needed to be at least 18 years of age, have measurable disease by RECIST v1.1 criteria, an ECOG performance status of 0 to 2, and acceptable hematologic, renal, and hepatic function. They must have received at least 1 prior line of systemic treatment as well as ICI therapy if approved for that specific tumor type; however, prior ICI exposure was not needed if it was not FDA-approved for that indication.

Those who had previously received an investigational agent, chemotherapy, immunotherapy, or radiotherapy within 28 days before the first dose of study treatment were excluded, unless investigators determined that all residual treatment-related adverse effects (AEs) were resolved or minimal and the patient was otherwise eligible to participate. They could not have experienced intolerance or life-threatening AEs from previous ICI therapy, nor could they have undergone a major surgical procedure within the 28 days before study treatment. They could not have known active brain or central nervous system metastases.

Participants received bintrafusp alfa intravenously at 1200 mg every 2 weeks, PDS0301 subcutaneously at 16.8 mcg/kg every 4 weeks or 8 mcg/kg every 2 weeks, and PDS0101 via two subcutaneous injections of 0.5 mL every 4 weeks.3 Dose reductions or skipped doses for toxicities were permitted for bintrafusp alfa and PDS0301.

The primary end point was ORR and secondary end points included safety, PFS, and OS, among others.

Prior findings from the study were released in December 2022 and showed that the triplet combination resulted in a median OS of 21 months for ICI-refractory patients (n = 29). In the ICI-naive patients, the median OS was NR.4

In the phase 2 VERSATILE-002 trial (NCT04260126), the combination of PDS0101 and pembrolizumab (Keytruda) led to a 2-year OS rate of 74% in patients with unresectable, recurrent or metastatic, HPV16-positive head and neck squamous cell carcinoma who were ICI-naive (n = 52).5 The 1-year OS rate in this population was 80%. Moreover, the doublet induced a confirmed overall response rate of 27% with 60% of patients experiencing tumor reduction. The median PFS in this group was 8.1 months.

“The ICI-resistant data from the VERSATILE-002 trial evaluating PDS0101 in combination with pembrolizumab that were reported October 3, 2023, further clarify the path forward for a potential registrational clinical trial of PDS0101 and PDS0301 in combination with a commercial ICI,” Bedu-Addo added in the news release.1 “With this exciting information, we will be finalizing the regulatory and clinical pathway for the triple combination with OS as the primary end point.”


  1. PDS Biotech announces updated survival data from NCI-led phase 2 clinical trial of PDS0101-based triple combination therapy in advanced HPV16-positive cancer patients which show 75% survival of ICI naïve patients at 36 months. News release. PDS Biotechnology Corporation. November 9, 2023. Accessed November 9, 2023. https://www.pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/125-2023-news/885-iotechnnouncespdatedurvivalatafromedh20231109
  2. Combination immunotherapy in subjects with advanced HPV associated malignancies. ClinicalTrials.gov. August 22, 2023. Accessed November 9, 2023. https://clinicaltrials.gov/study/NCT04287868
  3. Strauss J, Floudas CS, Sater HA, et al. Phase II evaluation of the triple combination of PDS0101, M9241, and bintrafusp alfa in patients with HPV 16 positive malignancies. J Clin Oncol. 2021;39(suppl 15):2501. doi:10.1200/JCO.2021.39.15_suppl.2501
  4. 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 November 9, 2023. https://www.pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/118-2022-news/758-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
  5. PDS Biotech announces interim 24-month survival rate of 74% in immune checkpoint inhibitor naïve head and neck cancer patients treated with PDS0101 in combination with Keytruda (pembrolizumab). News release. PDS Biotechnology. October 3, 2023. November 9, 2023. https://pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/125-2023-news/878-iotechnnouncesnterim24onthurvivalateof7420231003

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