298 - IMMUNOCERV Phase II Trial Combining the HPV-Specific T Cell Immunotherapy PDS0101 with Chemoradiation for Treatment of Locally Advanced Cervical Cancer

A. Grippin¹, K. Court², M. OHara², O. Gjyshi³, G. Mathew², M. Domingo⁴, L. L. Lin⁵, A. Jhingran¹, M. M. Joyner⁶, T. Cisneros Napravnik¹, K. Schmeler⁷, M. Hernandez², E. J. Lynn¹, A. Seo⁵, S. A. Copling⁸, L. Colbert¹, J. Sastry⁹, and A. H. Klopp¹; ¹Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ²The University of Texas MD Anderson Cancer Center, Houston, TX, ³Department of Radiation Oncology, Saint Elizabeth Cancer Center, Edgewood, KY, ⁴Department of Gynecologic Research, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁵Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁶Department of Breast Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁷Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁸UTHealth Houston McGovern Medical School, Houston, TX, ⁹MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Although expression of E6/E7 antigens by HPV-related cancers presents an opportunity for immunologic targeting, there are currently no HPV-specific FDA-approved immunotherapies to treat HPV-related cancers. The IMMUNOCERV trial was designed to test the hypothesis that PDS0101, a novel, subcutaneously administered HPV-specific vaccine containing peptide pools encoding E6/E7 antigens, would be safe and effective in combination with standard of care chemoradiation for locally advanced HPV-related cervical cancer. Materials/

Methods: In this single-arm, phase 2 study (NCT04580771), patients received PDS0101 at Day -10, 7, 28, and 49 (+/- 5 days) in relation to the start of chemoradiation. Key eligibility criteria included newly diagnosed, biopsy-proven locally advanced squamous cell carcinoma of the cervix (tumor =5cm and/or nodal disease), age greater than 17, and ECOG =2. The trial was designed to include 35 patients. Adverse events were assessed using the CTCAE version 5.0. The primary endpoint for this study was the rate of clinically significant grade =3 acute toxicities from first vaccine injection up to 30 days following completion of chemoradiation (Day -10 to day 80). Prespecified secondary endpoints included the rate of complete metabolic response (CMR) on Day 170 PET CT (± 14 days), rate of =90% gross tumor volume reduction (GTVR) on Day 35 MRI (± 5 days), progression-free survival (PFS), and overall survival (OS) at 12 and 18 months after completion of chemoradiation.

Results: Seventeen patients were enrolled before the trial was closed due to a change in the standard of care. Median follow up was 575 days. Acute grade 3+ adverse events occurred in eight patients (47%). Toxicities related to PDS0101 injection were limited to injection site reaction in twelve patients (71%) and single reports of urticarial allergic reaction (Grade 3) and pain (Grade 2). Five patients (29%) experienced >90% GTVR at Day 35 MRI compared to baseline. CMR at 4 month follow up were achieved in 10 of 17 patients (59%) including seven patients who completed all five prescribed doses of PDS0101 (88%). Twelve, 18, and 36-month PFS were 82.4%, 74.9%, and 74.9%. Twelve, 18, and 36-month DFS were each 82.35%. OS at 12, 18, and 36 months was 92.9%, 84.4%, and 84.4%. GTVR on Day 35 MRI >75% (HR 0.064, 95% CI 0.004-0.92, p=0.001) and receipt of all five doses of PDS0101 (HR 0.27, 95% CI 0.02-0.91, p=0.040) were associated with improved PFS. All patients who received five doses of PDS0101 were disease free and alive at 36 months.

Conclusion: In this final report of the IMMUNOCERV clinical trial, PDS0101 was safe and well-tolerated, and receipt of all prescribed doses of PDS0101 was associated with improved PFS. Further investigation of PDS0101 in cervical cancer in combination with pembrolizumab is warranted.