PDS Biotechnology Announces Achievement of Efficacy Threshold in Stage 2 of the VERSATILE-002 Trial Evaluating PDS0101 & KEYTRUDA in Head & Neck Cancer

PDS Biotechnology Corporation recently announced it achieved the threshold for efficacy as per investigator assessment in Stage 2 of the VERSATILE-002 (NCT04260126) Phase 2 clinical trial investigating PDS0101 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), for the treatment of unresectable, recurrent or metastatic human papillomavirus (HPV)16-positive head and neck cancer. The achievement of full recruitment of 54 patients in the ICI naïve arm was announced in May 2023. The threshold for efficacy, as defined in the clinical protocol, was achieved when 14 out of the 54 immune checkpoint inhibitor (ICI) naïve patients enrolled achieved a confirmed objective response. Additional patients in the trial have yet to undergo imaging evaluation.

Per RECIST 1.1, the standard to classify oncologic imaging outcomes in clinical trials, patients are considered to have achieved an objective response when imaging studies document tumor shrinkage of 30% or more. In VERSATILE-002, the primary endpoint requires two consecutive scans 9 to 12 weeks apart, rather than one, to be considered a confirmed objective response. Confirmation with two consecutive scans is not required to achieve an objective response in every clinical trial per RECIST 1.1.

At the recent 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, we presented data showing 9 confirmed responses among 34 evaluable patients.  Median progression-free survival (PFS) of 10.4 months was also presented at the 2023 ASCO Annual Meeting along with a 12-month overall survival (OS) rate of 87.1% for patients with a CPS≥1. Additional patients have been assessed since data was presented at the 2023 ASCO Annual Meeting. With these additional data, a total of 14 patients have now achieved a confirmed response to date.   The achievement of this endpoint suggests an additive effect of PDS0101 over published results with ICI monotherapy and is based on statistical calculations using the appropriate power and alpha.

The primary endpoint in the VERSATILE-002 study is the best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST 1.1. The key secondary endpoints are progression-free survival (PFS), OS at 12 and 24 months, safety, and tolerability. The study utilizes a Simon’s 2-stage optimum design.

“We are highly encouraged by the growing set of PDS0101 efficacy and safety data being generated in multiple independent trials by leading experts in the field,” stated Dr. Frank Bedu-Addo, President and Chief Executive Officer of PDS Biotech. “The consistency in PDS0101 induced HPV16-specific immune responses, the response rates and survival benefit observed in multiple types of HPV cancer and at different stages of disease, aligns with both the preclinical and Phase 1 monotherapy results. Multiple studies have demonstrated the induction of high levels of active and potent, HPV16-specific CD4 and CD8 T cells, as well as long-lasting memory CD8 T cells by PDS0101.”

“Achieving the efficacy threshold in VERSATILE-002 is an important milestone for the Company, especially as it has been achieved ahead of the full efficacy evaluation for this cohort,” stated Dr. Lauren V. Wood, Chief Medical Officer of PDS Biotech. “With our Phase 2 trial near completion, and our planned global Phase 3 confirmatory randomized, controlled trial, VERSATILE-003, actively advancing, we believe we are closer to our goal of providing a well-tolerated, safe and effective therapy for those who suffer from head and neck cancer, a critical unmet medical need.”

PDS Biotech plans to initiate the VERSATILE-003 as a result of the successful completion of an End-of-Phase 2 meeting in the third quarter of 2022 with the FDA, during which PDS Biotech received guidance on key elements of the Phase 3 program that will support the submission of a Biologics License Application (BLA). The planned primary endpoints for VERSATILE-003 are OS and PFS. In preparation for the VERSATILE-003 trial, PDS Biotech plans to submit an amended Investigational New Drug (IND) application to the FDA in the third quarter of 2023.

PDS0101, PDS Biotech’s lead candidate, is a novel investigational human papillomavirus (HPV)-targeted immunotherapy that stimulates a potent targeted T cell attack against HPV-positive cancers. PDS0101 is given by subcutaneous injection alone or in combination with other immunotherapies and cancer treatments. In a Phase 1 study of PDS0101 in monotherapy, the treatment demonstrated the ability to generate multifunctional HPV16-targeted CD8 and CD4 T cells with minimal toxicity. Interim data suggests PDS0101 generates clinically effective immune responses and the combination of PDS0101 with other treatments can demonstrate significant disease control by reducing or shrinking tumors, delaying disease progression, and/or prolonging survival. The combination of PDS0101 with other treatments does not appear to compound the toxicity of other agents.

VERSATILE-002 is a single-arm Phase 2 trial evaluating the safety and efficacy of PDS0101, an HPV16-targeted investigational T cell-activating immunotherapy that leverages PDS Biotech’s proprietary Versamune technology, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab). The combination is being evaluated in immune checkpoint inhibitor (ICI)-naïve and ICI-refractory patients with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC) and was granted Fast Track designation by the Food and Drug Administration in June 2022.

Interim efficacy and safety data were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting for ICI-naïve patients (PR link). Preliminary data from the first 34 patients demonstrated a 12-month overall survival rate of 87% and median progression free survival of 10.4 months. No Grade 4 or higher treatment related adverse events were observed.

VERSATILE-003 is a randomized, controlled Phase 3 trial evaluating the safety and efficacy of PDS0101 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) versus KEYTRUDA monotherapy. The combination is being evaluated in immune checkpoint inhibitor (ICI)-naïve patients with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC) and was granted Fast Track designation by the Food and Drug Administration in June 2022.

Versamune is a novel investigational T cell activating platform which effectively stimulates a precise immune system response to a cancer-specific protein. Versamune-based investigational immunotherapies promote a potent targeted T cell attack against cancers expressing the protein. They are given by subcutaneous injection and can be combined with standard of care treatments. Clinical data suggest that Versamune-based investigational immunotherapies, such as PDS0101, demonstrate meaningful disease control by reducing and shrinking tumors, delaying disease progression and/or prolonging survival. Versamune-based immunotherapies have demonstrated minimal toxicity to date that may allow them to be safely combined with other treatments. We believe Versamune-based investigational immunotherapies represent a transformative treatment approach for cancer patients to provide improved efficacy, safety and tolerability.

PDS Biotech is a clinical-stage immunotherapy company developing a growing pipeline of targeted cancer and infectious disease immunotherapies based on our proprietary Versamune, Versamune plus PDS0301, and Infectimune T cell-activating platforms. We believe our targeted immunotherapies have the potential to overcome the limitations of current immunotherapy approaches through the activation of the right type, quantity and potency of T cells. To date, our lead Versamune clinical candidate, PDS0101, has demonstrated the ability to reduce and shrink tumors and stabilize disease in combination with approved and investigational therapeutics in patients with a broad range of HPV16-associated cancers in multiple Phase 2 clinical trials and will be advancing into a Phase 3 clinical trial in combination with KEYTRUDA for the treatment of recurrent/metastatic HPV16-positive head and neck cancer in 2023. Our Infectimune-based vaccines have also demonstrated the potential to induce not only robust and durable neutralizing antibody responses, but also powerful T cell responses, including long-lasting memory T cell responses in pre-clinical studies to date. For more information, visit www.pdsbiotech.com.