Recruitment to Phase 2 Trial Examining PDS0101 Triplet in HPV Cancers Temporarily Suspended


The clinical-stage immunotherapy company PDS Biotechnology Corporation has announced the temporary suspension of recruitment to the National Cancer Institute–led phase 2 trial, which is evaluating a novel triplet combination comprised of PDS0101 and 2 immunomodulating agents in patients with advanced human papillomavirus cancers.

The clinical-stage immunotherapy company PDS Biotechnology Corporation has announced the temporary suspension of recruitment to the National Cancer Institute (NCI)–led phase 2 trial (NCT04287868), which is evaluating a novel triplet combination comprised of PDS0101 (Versamune-HPV16) and 2 immunomodulating agents in patients with advanced human papillomavirus (HPV) cancers.1

Although the issue has not been disclosed, the company specified that it is not specific to the trial, nor is it associated with any safety or efficacy concerns with the regimen. Moreover, the issue is expected to resolve in a timely manner, and the timing of clinical data produced in the trial is not anticipated to be affected by the suspension.

“We know from the interim data that this combination has the potential to significantly improve clinical outcomes for patients with advanced, refractory HPV16-associated cancers who have limited treatment options,” Lauren V. Wood, MD, chief medical officer at PDS Biotechnology, stated in a press release. “While the trial is experiencing a slight administrative delay, we are pleased to report that the PDS0101 trial recruitment has progressed well, and it is anticipated that it will resume recruitment shortly. We believe, based on the previously reported results, that this treatment could significantly improve survival benefit for these patients, and we look forward to resumption of the trial in the near term.”

PDS0101 is a micellar multipeptide-based therapeutic vaccine that targets HPV16 E6/E7.2 The Versamune particles include the cationic lipid R-DOTAP which upregulates type I interferons and encourages antigen cross-presentation. Moreover, bintrafusp alfa (M7824) is a bifunctional fusion protein comprised of the extracellular domain of the TGF-β, which is fused to a human IgG1 monoclonal antibody that blocks PD-L1. The tumor-targeting IL12 immunocytokine M9241 (NHSIL12) is composed of 2 IL12 heterodimers fused to a NHS76 antibody which binds to histones on free DNA fragments found in areas of tumor necrosis.

Previously, preclinical research was conducted to evaluate the 3 agents either alone or in doublet or triplet combinations utilizing a TC-1 HPV16-positive tumor model. The 3-drug regimen resulted in the maximum HPV-specific immune response, T-cell infiltration in the tumor microenvironment, and tumor reduction.

The phase 2 study enrolled patients with advanced HPV-related cancers such as cervical cancer, anal cancer, and P16-positive oropharyngeal cancer, among others.

Investigators administered bintrafusp alfa at a flat intravenous dose of 1200 mg every 2 weeks, M9241 at a subcutaneous dose of 16.8 mcg/kg every 4 weeks, and PDS0101, which was administered as 2 separate subcutaneous injections at 0.5 mL every 4 weeks.

Participants received treatment until confirmed disease progression, intolerable toxicity, or any criteria were met for withdrawal. Treatment past progression was permitted, as were dose reductions of M9241 to 8 mcg/kg and skipped doses of any agents due to toxicities.

The primary end point of the trial was objective response rate (ORR), and a key secondary end point was safety.

At a data cutoff of March 1, 2021, a total of 25 patients had been given the triplet regimen. The median age for participants was 50 years (range, 37-80) and 68% were female. Moreover, 40% had cervical cancer, 24% had anal cancer, 24% had head and neck squamous cell carcinoma, and 12% had vulvar or vaginal cancer. Seventy-two percent of patients had HPV 16 status, 24% had HPV type other than 16, and 4% were HPV negative.

Regarding number of prior therapies received, 20% had previously received 1 therapy, 44% had received 2, and 36% had received 3 or more therapies. All patients previously received chemotherapy, 96% had received radiotherapy, and 56% had received a PD-1/PD-L1 inhibitor.

At a median follow-up of 8 months, the triplet elicited an ORR of 40% in the 25 patients, with a 52% disease reduction, 80% of patients in ongoing response to treatment, and an overall survival (OS) rate of 80%.

Among those with HPV 16-positive disease (n = 18), the ORR was 55.6%, which consisted of a complete response (CR) rate of 11.1% and a partial response (PR) rate of 44.4%. The disease reduction rate was 66.7%, 80% of patients were still responding to treatment, and the OS rate was 88.9%.

In checkpoint inhibitor-naïve patients with HPV-16 positive disease (n = 6), the regimen induced an ORR of 83.3%, which was comprised of a 16.7% CR rate and a 66.7% PR rate. The disease reduction rate was 83.3%, 80.0% were experiencing ongoing response, and the OS rate was 100%.

Lastly, in patients with HPV 16-positive disease who were refractory to checkpoint inhibitors (n = 12), the combination elicited an ORR of 41.7%, with a CR rate of 8.3% and a PR rate of 33.3%. Moreover, 58.3% of patients experienced disease reduction, 80.0% were experiencing an ongoing response to treatment, and the OS rate was 83.3%.

Notably, responses to treatment were noted to have occurred irrespective of tumor type in patients with HPV 16-positive disease. Moreover, most of the patients with HPV16-positive disease who were naïve to checkpoint inhibitors responded to treatment, and most of those who were refractory to checkpoint inhibitors experienced tumor reduction.

Regarding safety, 92% of patients experienced treatment-related adverse effects (TRAEs), and 20% of these toxicities resulted in discontinuation. Forty percent of patients experienced TRAEs that were grade 3 in severity, and they included anemia due to hematuria (n = 4), aspartate

aminotransferase/alanine aminotransferase elevation (n = 2), flu-like symptoms (n = 1), nausea/vomiting (n = 1), leukopenia (n = 1), lymphopenia (n = 1), and hemophagocytic lymphohistiocytosis (n = 1).

All 4 patients who experienced grade 3 hematuria had cervical cancer and previously received pelvic radiotherapy and brachytherapy. One patient with transient grade 3 leukopenia and lymphopenia also experienced transient grade 4 neutropenia. Notably, no treatment-related deaths were reported.


  1. PDS Biotech provides update on National Cancer Institute–led phase 2 clinical trial of PDS0101-based combination. News release. PDS Biotechnology Corporation. October 21, 2021. Accessed October 29, 2021.
  2. 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

This article was originally published on OncLive®.

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