Abstract CT091: Trial in progress: A phase I study of personalized neoantigen vaccination combined with PD-1 blockade and CD40 agonism in resected pancreatic ductal adenocarcinoma

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal even in localized stages, with frequent recurrence despite curative-intent resection and perioperative chemotherapy. Personalized neoantigen vaccination offers a promising strategy to elicit tumor-specific T cell responses against micrometastatic disease in the adjuvant setting. Our personalized peptide-based vaccine platform - termed NeoAg-VAX - targets up to 10 neoantigens per patient and has demonstrated favorable safety and immunogenicity across solid tumors, including lung and colorectal cancer (Li F et al, JITC 2021; Haldar SD et al, AACR 2025). However, PDAC has a profoundly “cold,” immunosuppressive microenvironment that can limit effective priming and durability of vaccine-induced antitumor immunity, supporting rational combinations with PD-1 blockade and CD40 agonism to enhance antigen presentation and reinvigorate effector function. Methods: This study is a single-center, non-randomized, open-label, investigator-initiated phase 1 trial of NeoAg-VAX in combination with anti-PD-1 pembrolizumab +/- CD40 agonist APX005M in patients with surgically resected PDAC. Whole exome/RNA sequencing of resected tumor tissue is performed with HLA binding prediction to identify patient-specific neoantigen peptides for vaccine formulation. Key eligibility criteria include complete R0/R1 resection, receipt of >1 line of standard chemotherapy, adequate organ/marrow function, and ECOG 0-1. The co-primary endpoints are safety and feasibility. Secondary endpoints include immunogenicity, ctDNA clearance, RFS, and OS. Vaccines are given subcutaneously (SQ) with topical imiquimod adjuvant and APX005M (0.3 mg/kg IV + 250 µg SQ) on weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Pembrolizumab 200 mg IV is given every 3 weeks during weeks 3-24. Although drug supply for APX005M was terminated in August 2023, accrual for vaccine plus anti-PD-1 therapy has continued thereafter. Translational studies evaluating vaccine-induced ctDNA dynamics and functional neoantigen-specific T cell responses are in progress. As of January 2026, 6 patients have been vaccinated in this cohort with follow-up and analyses ongoing (NCT02600949). Citation Format: S. Daniel Haldar, Jason Willis, Arjun Katailiha, Amjad Talukder, Brandon Smaglo, Nicole Balmaceda, Camila Braganca Xavier, Dan Zhao, M. Pia Morelli, Ryan Huey, Chandrikha Chandrasekharan, Florencia McAllister, Shubham Pant, Jane Thomas, Anirban Maitra, Scott Kopetz, Greg Lizee, Michael J. Overman. Trial in progress: A phase I study of personalized neoantigen vaccination combined with PD-1 blockade and CD40 agonism in resected pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT091.