PDS0101 and CRT Displays Encouraging Early Data in Cervical Cancer

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The combination of PDS0101 with standard-of-care (SOC) chemoradiotherapy (CRT) was associated with a rapid decline in human papillomavirus (HPV) circulating cell-free DNA (cfHPV-DNA), suggesting a potential predictive biomarker of treatment response, according to findings from the phase 2 IMMUNOCERV clinical trial (NCT04580771).¹

Findings from the study were presented at ASTRO 2023 and showed that HPV16 was detected in 59% of tumors and 70% of cfDNA. The median cfDNA at baseline was 28.15 copies/mL (range, 0-206,030 copies/mL). There was an earlier and greater proportion of cfDNA clearance observed with PDS0101 and chemoradiation (CRT) compared with SOC CRT alone at 81.3% clearance after 3 weeks vs 30.3% with SOC (P =.0018). At 5 weeks, there was 91.7% of clearance with the combination vs 53.1% with SOC (P =.0179).

Additionally, all of the patients who were treated with PDS0101 had cancer that had spread to the lymph nodes and overall, baseline cfDNA levels correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node involvement.

“We are encouraged by this data from the IMMUNOCERV trial, which highlight the potential of PDS0101 to positively impact cfDNA, an emerging biomarker of clinical response in cervical and other HPV-related cancers,” said Lauren V. Wood, MD, chief medical officer of PDS Biotech, in a press release. “The findings complement previously presented IMMUNOCERV data which suggested PDS0101 promotes the induction of multifunctional CD8 killer T cells that were associated with declines in circulating tumor DNA and a clinical response with greater than 60% tumor shrinkage at mid-point evaluation in 100% of high-risk cervical cancer patients on the trial. We look forward to continuing to address the unmet needs of patients suffering from HPV-positive cancers such as cervical cancer.”

PDS0101 is a novel investigational HPV-targeted immunotherapy which works by stimulating a potent targeted T-cell attack against cancers. The therapy is given to patients as a subcutaneous injection alone or in combination with other immunotherapies.

In a phase 1 study which evaluated PDS0101 as a monotherapy, PDS0101 demonstrated the ability to generate multifunctional HPV16-targeted CD8 and CD4 T cells with minimal toxicity. Based on interim data, PDS0101 can potentially produce clinically active immune responses. When given in combination, PDS0101 can also demonstrate significant disease control by reducing or shrinking tumors, delaying disease progression and/or prolonging survival. Additionally, PDS0101 given with other therapies has not shown to compound the toxicity of other agents.

The IMMUNOCERV trial is investigating PDS0101 in combination with SOC CRT. Investigators are evaluating the relationship between the levels of circulating cfHPV-DNA along with the extent of disease, clinical staging, and treatment response in patients with HPV-positive cervical cancer who have large tumors over 5 cm in size and/or cancer that has spread to the lymph nodes.²

In the experimental arm of the study, patients are undergoing radiation therapy over 1 hour on Monday-Friday for 5-7 weeks. They will receive cisplatin via intravenous infusion over 4 hours once a week during the 5 weeks of radiation therapy in the absence of disease progression and unacceptable toxicity, as well as PDS0101 on days 10, 7, 28, 49, and 170.

Enrollment in the study is open to patients with newly diagnosed locally advanced squamous cell carcinoma of cervix who have a WHO/ECOG performance status of 0, 1, or 2, alanine aminotransferase, aspartate aminotransferase, and total bilirubin = < 2-fold the upper limit of normal. Additionally, patients must not have current malignancies at other sites, excluding adequately treated basal or squamous cell carcinoma of the skin, and patients are eligible for the study if they have previously received a potentially curative therapy for a malignancy who have no evidence of that disease for 5 years and who are deemed at low-risk for recurrence.

The primary end point of the study is to evaluate the safety and toxicity profile of PDS0101 with SOC CRT, and secondary end points include the rate of complete metabolic response on day 170 PET CT, rate of >= 90% gross tumor volume reduction day 35 MRI, rates of local control, progression-free survival, overall survival, and long-term safety.

Exploratory end points are also being assessed in the study, including enzyme-linked immunosorbent spot assays on interferon-gamma and granzyme B levels in E6/7-specific T cells isolated from peripheral blood mononuclear cells, intratumoral T-cell receptor clonality at baseline compared with at the end of treatment by TCR sequencing, measure of CD4-positive and CD8-positive tumor-infiltrating lymphocytes, intestinal and cervical microbiome by analyzing rectal and cervical swab samples with 16s ribosomal ribonucleic acid sequencing, and additional assays, including circulating tumor cells, and circulating cell-free tumor DNA.

“HPV16 cfDNA represents a novel biomarker with the potential to help oncologists make more informed treatment decisions for their patients with HPV16-positive cancers. These early data are encouraging, and we will continue to evaluate patients to determine any potential correlations between cfDNA clearance and clinical outcomes. Further analysis of cfDNA kinetics could provide valuable information on the relationship between cfDNA levels, treatment response, and ongoing clinical outcomes,” said study principal investigator Ann Klopp, MD, PhD, professor of radiation oncology at MD Anderson Cancer Center, in the press release.1 “I look forward to the continued evaluation of PDS0101 in combination with standard-of-care chemoradiotherapy.”

REFERENCES:

1. PDS Biotech announces PDS0101 combined with chemoradiotherapy associated with rapid decline in circulating tumor DNA (ctDNA/cfDNA). News release. PDS Biotechnology Corporation. October 3, 2023. Accessed October 4, 2023.

2. A vaccine (PDS0101) and chemoradiation for the treatment of stage IB3-IVA cervical cancer, the IMMUNOCERV trial. ClinicalTrials.gov. Updated April 7, 2023. Accessed October 4, 2023. https://tinyurl.com/h32m9zsv