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Survival benefits were observed in patients with human papillomavirus (HPV) 16-positive cancers who are immune checkpoint inhibitor (ICI)-naïve and ICI-resistant when treated with PDS0101, an investigational immunotherapy, and PDS0301(M9241, NHS-IL12), an IL-12 antibody-drug conjugate, and bintrafusp alfa(M7824), an investigational ICI, according to final survival data from a phase 2 trial (NCT04287868) led by the National Cancer Institute.¹

In the ICI-naïve population, 75% (n = 8) patients who received this triple combination were still alive at 36 months, and the median overall survival (OS) was not yet reached. This compares with published data on standard-of-care that reports 30%-50% of patients in this population are alive at 12 months, and less than 30% remain alive at 24 months, according to PDS Biotechnology.

In patients who were ICI-resistant, the triple combination demonstrated a median OS of approximately 20 months and the median OSat 12 months was 72%. The 8 patients given PDS0101 with PDS0301 and high doses of ICI had an overall response rate (ORR) of 63%. Among the 21 patients given PDS0101 combined with low doses of ICI and/or PDS0301, the ORR was only 5%.

“We are encouraged by the survival rates for both ICI-naïve and ICI-resistant patients with HPV16-positive cancers who were treated with the triple combination therapy,” said Frank Bedu-Addo, PhD, chief executive officer of PDS Biotechnology, in a press release.¹ “With this exciting information, we will be finalizing the regulatory and clinical pathway for the triple combination with OS as the primary endpoint.”

About the Phase 2 Study

In the phase 2 trial sponsored by the National Cancer Institute, investigators are evaluating the triple combination of PDS0101, PDS0301, and bintrafusp alfa in patients with cytologically or histologically confirmed locally advanced or metastatic HPV-associated malignancies. Patients are being evaluated to assess the primary end point of ORR, along with secondary end points of progression-free survival, OS, and more.²

HPV-associated malignancies consisted of cervical cancers, cyclin-dependent kinase inhibitor 2A oropharyngeal cancers, anal cancers, vulvar, vaginal, penile, and squamous cell rectal cancers, as well as other solid tumors, including lung or esophageal cancers.²

Enrollment in the study was open to patients aged 18 years or older with measurable disease by RECIST v1.1 criteria. Patients were required to have an ECOG performance status of 0 to 2, and acceptable hematologic, renal, and hepatic function, and they must have been treated with 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.

Once enrolled, patients were given PDS0101 via 2 subcutaneous injections of 0.5 mL every 4 weeks in addition to PDS0301 subcutaneously at 16.8 mcg/kg every 4 weeks or 8 mcg/kg every 2 weeks, and bintrafusp alfa via intravenous infusion at 1200 mg every 2 weeks.

Prior Data of PDS0101

Previous interim data from the trial found that the triple combination led to a median OS of 21 months in 29 patients with ICI-resistant disease. In the ICI-naive patients. The median OS had not yet been reached. These findings show a significant improvement vs the historical median OS in this patient population at 3-4 months.

At the time of this interim analysis, 50 patients were enrolled, including 37 patients with HPV16-positive evaluable disease and 29 patients who have also failed treatment with CPIs.

Additional findings showed that for safety, 48% (n = 24) of all patients experienced grade 3 treatment-related adverse events (AEs), and 4% (n = 2) had severe grade 4 AEs. Among patients treated with the combination of ICIs and chemotherapy, approximately 70% of patients had grade 3 or higher treatment-related AEs.

In another study, VERSATILE-002 trial (NCT04260126), PDS0101 given in combination with pembrolizumab (Keytruda) elicited a 2-year OS rate of 74% among patients with unresectable, recurrent or metastatic, HPV16-positive head and neck squamous cell carcinoma who were ICI-naive. These results come from 52 patients enrolled in the phase 2 study.

At 1-year, the OS rate was 80% and the combination generated a confirmed ORR of 27% with 60% of patients experiencing tumor reduction. In this group, the median PFS was 8.1 months.

Data from the phase 2 VERSATILE-002 trial further support the potential of PDS0101 given as a combination therapy with an ICI.

“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,” said Bedu-Addo in the press 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.”

REFERENCES

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 10, 2023. https://tinyurl.com/mwcx4355

2. Combination immunotherapy in subjects with advanced HPV associated malignancies. ClinicalTrials.gov. August 22, 2023. Accessed November 10, 2023. https://clinicaltrials.gov/study/NCT04287868

3. 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 10, 2023. https://bit.ly/3Gds1OF

4. 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 Corporation. October 3, 2023. Accessed November 10, 2023. https://tinyurl.com/4bzpbdt7