Abstract A070: CENDIFOX: Phase I/II Trial of CEND-1 (LSTA1, certepetide) with Neoadjuvant mFOLFIRINOX in Resectable and Borderline Resectable PDAC

Abstract

Background: Certepetide (aka CEND-1, LSTA1) is a tumor-penetrating peptide that binds integrin αvβ3 on tumor endothelium and neuropilin-1, triggering transcytosis to enhance intratumoral drug delivery and modulate the tumor microenvironment (TME). We report findings from resectable and borderline resectable PDAC of the CENDIFOX trial evaluating Certepetide plus mFOLFIRINOX as neoadjuvant therapy. Methods: Eligible patients with resectable and borderline resectable PDAC received neoadjuvant mFOLFIRINOX for 3 cycles followed by addition of Certepetide (3.2 mg/kg IV on Day 1) to mFOLFIRINOX every 2 weeks from cycles 4 onward for at least 6 cycles, followed by evaluation for resection. The primary objective was safety; secondary endpoints included resection rate, pathologic response, PFS, OS, and immune profiling. Correlative biopsies were obtained pre-treatment and at end of therapy. Results: 35 patients were enrolled. No dose-limiting toxicities were observed. Common Grade ≥3 AEs included neutropenia, mucositis, fatigue, anorexia, and gastrointestinal events. Toxicities were manageable with dose reductions or delays. Most AEs were attributed to mFOLFIRINOX; no serious AEs were attributed to Certepetide. Of the 35 patients enrolled, 10 underwent pancreatic cancer resection following treatment regimen. Among these evaluable cases, the pathologic partial response rate (Tumor Regression Grade 2) was 70%, and the R0 resection rate was 50%. At limited follow-up, the 2-year OS rate was 60% (95% CI, 26%–100%), and median DFS was 12 months (95% CI, 10–NA). Immunofluorescence staining of PDAC tissue demonstrated increased post-treatment expression of CD68 (tumor-associated macrophages, TAMs) and immune checkpoints PD-1/PD-L1. Mean log-transformed CD68 intensity increased from 13.96 to 15.20; PD-1 from 12.94 to 13.57; and PD-L1 from 13.33 to 13.54, suggesting enhanced immune infiltration. Conclusions: Certepetide combined with mFOLFIRINOX is safe and feasible in resectable PDAC. Encouraging early OS and PFS data, high pathologic partial response rates, and correlative immune findings support further evaluation in randomized trials. Enhancement of TAMs and PD-1/PD-L1 in the tumor microenvironment supports the potential to convert PDAC from an immune-cold to an immune-hot tumor, possibly sensitizing it to immunotherapy. Trial Identifier: NCT05121038 Citation Format: Anup Kasi, Raed Al-Rajabi, Anwaar Saeed, Jianzheng Wu, Milind Phadnis, Shannon Bradbury, Stacey Krepel, Subhrajit Saha, Grace Li Haug, Prasad Dandawate, Rashna Madan, Mojtaba Olyaee, Amit Rastogi, Timothy Schmitt, Sean Kumer, Weijing Sun, Joaquina Baranda. CENDIFOX: Phase I/II Trial of CEND-1 (LSTA1, certepetide) with Neoadjuvant mFOLFIRINOX in Resectable and Borderline Resectable PDAC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3): nr A070.