PDS0101 Plus Pembrolizumab Elicits 74% 2-Year OS Rate in ICI-Naïve, HPV16+ HNSCC

Frank Bedu-Addo, PhD

The addition of PDS0101 to pembrolizumab (Keytruda) resulted in a 2-year overall survival (OS) rate of 74% in patients with unresectable, recurrent, or metastatic, HPV16-positive head and neck squamous cell carcinoma (HNSCC) who were naïve to an immune checkpoint inhibitor (ICI), according to updated data from the phase 2 VERSATILE-002 trial (NCT04260126).¹

Further updated interim data from showed that the efficacy-evaluable, ICI-naïve patient population (n = 52) experienced a 1-year OS rate of 80%. Additionally, PDS0101 plus pembrolizumab elicited a confirmed overall response rate (ORR) of 27%, and 60% of patients experienced tumor shrinkage. The median progression-free survival (PFS) for the ICI-naïve population was 8.1 months.

“The updated interim data from our VERSATILE-002 clinical trial further validates the potential of PDS0101 when combined with [pembrolizumab] to address the urgent need for more effective therapies that are well tolerated and allow [patients with] advanced, recurrent, and metastatic HPV16-positive HNSCC to live significantly longer lives than current approaches,” Frank Bedu-Addo, PhD, president and chief executive officer of PDS Biotechnology, stated in a news release.

Additional data from VERSATILE-002 in a cohort of patients with ICI-pretreated, unresectable, recurrent, or metastatic, HPV16-positive HNSCC showed that efficacy-evaluable patients (n = 21) achieved a 1-year OS rate of 56%. The confirmed ORR in this population was 0%; however, PDS Biotechnology, the developer of PDS0101, said in an announcement that the ORR data suggest that the agent’s impact on survival does not appear to be dependent on tumor shrinkage.

“We are pleased with the OS results and knowledge gained from the ICI-refractory cohort of VERSATILE-002. In agreement with our data monitoring committee, we will not progress to stage 2 of this cohort in VERSATILE-002. As previously announced, we have no plans to further develop this combination for ICI refractory patients,” Lauren V. Wood, MD, chief medical officer of PDS Biotechnology, said in a news release. “PDS0101 appears to immunologically alter the patient’s tumor microenvironment to promote survival. This important data will help inform our development plans for PDS0101.”

PDS0101 is a novel, investigational, HPV-targeted immunotherapy designed to stimulate a potent targeted T-cell attack against HPV-positive cancers.

Previously reported data from the ICI-naïve cohort presented at the 2023 ASCO Annual Meeting showed that patients in the intention-to-treat (ITT) population (n = 48) achieved a 12-month OS rate of 87.1% and a median OS that was not evaluable (NE; 95% CI, 15.3-NE).² In the modified ITT population, which included patients who underwent imaging assessment after treatment (n = 34), the median PFS was 10.4 months (95% CI, 4.2-15.3).

The open-label, nonrandomized VERSATILE-002 trial enrolled patients at least 18 years of age with recurrent and/or metastatic, HPV-positive HNSCC. In the ICI-naïve cohort, patients were also required to have a combined positive score (CPS) of at least 1 and were not allowed to have prior treatment with an immunological therapy for metastatic disease.³

Patients in the ICI-pretreated cohort needed to have documented and radiologically confirmed clinical progression or recurrence after treatment with ICIs as a single agent or in combination. At least 2 doses of an ICI or a minimum of 6 weeks on treatment were required.

All patients were treated with 200 mg of intravenous pembrolizumab once every 3 weeks plus 2 subcutaneous injections of PDS001 at 0.5 mL given during cycles 1, 2, 3, 4, and 12 for a maximum of 5 doses.²

ORR served as the trial’s primary end point, and secondary end points consisted of PFS, OS, and safety.³

In evaluable patients in the ICI-naïve cohort (n = 55), 60% of patients had a combined positive score (CPS) of 1 to 19, and 40% had a CPS score of at least 20.¹

Regarding safety, 13% of evaluable patients in the ICI-naïve group (n = 62) experienced grade 3 treatment-related adverse effects (TRAEs). However, no grade 4 or 5 TRAEs were reported. In safety-evaluable patients in the ICI-pretreated cohort (n = 25), grade 3 TRAEs occurred in 4% of patients, and no patients experienced grade 4 or 5 TRAEs.

“Following feedback from the FDA, we look forward to evaluating this promising combination treatment in the [phase 3] VERSATILE-003 clinical trial, which we expect to initiate in the fourth quarter of 2023,” Bedu-Addo added. “VERSATILE-003 will investigate the efficacy and safety of PDS0101 combined with [pembrolizumab] compared to [pembrolizumab] monotherapy in ICI-naïve patients with recurrent or metastatic, HPV16-positive HNSCC. The primary endpoint for the study will be OS.”

References

1. 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. October 3, 2023. https://pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/125-2023-news/878-iotechnnouncesnterim24onthurvivalateof7420231003
2. Price KAR, Kaczmar JM, Worden FP, et al. Safety and efficacy of immune checkpoint inhibitor (ICI) naïve cohort from study of PDS0101 and pembrolizumab in HPV16-positive head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2023;41(suppl 16):6012. doi:10.1200/JCO.2023.41.16_suppl.6012
3. Study of PDS0101 and pembrolizumab combination I/​O in subjects with HPV16 + recurrent and/​or metastatic HNSCC (VERSATILE002). ClinicalTrials.gov. Updated June 22, 2023. Accessed October 3, 2023. https://clinicaltrials.gov/study/NCT04260126