260MO AGITG ASCEND study: Randomised, double-blind phase II study of certepetide (CERT) or placebo (PLA) added to gemcitabine plus nab-paclitaxel in patients with untreated metastatic pancreatic ductal adenocarcinoma (mPDAC): Cohort B progression-free survival (PFS) results.

Abstract

Background: CERT (aka LSTA1 or CEND-1) is a novel cyclic peptide that improves penetration of co-administered drugs into tumour and stroma, potentially leading to increased anti-neoplastic activity. ASCEND is a randomised phase 2 trial designed to investigate the impact of adding CERT either as a single IV dose (cohort A previously reported) or two IV doses of CERT/PLA separated by 4 hours (h) (cohort B) to gemcitabine (GEM) plus nab-paclitaxel (NPC) as first-line chemotherapy for mPDAC (NCT05042128). CERT's half-life in humans is ~1.5 h. Method(s): In cohort B 63 participants with mPDAC and ECOG 0-1 were randomised 2:1 to receive GEM/NPC plus IV CERT (3.2 mg/kg) or PLA, administered twice separated by 4 h, on days 1, 8, & 15 every 28-day cycle, with stratification was by age (< 65/>=65 years), ECOG (0/1), presence of liver metastases (Y/N), and trial site. Cohort B is exploratory and not powered to test a specific hypothesis. The primary outcome is 6-month (mo) PFS determined by the Kaplan-Meier method. Secondary outcomes were median PFS (mPFS), overall survival (OS), objective response rate (ORR), and toxicity. Result(s): Sixty-three patients (42 CERT, 21 PLA) were enrolled in cohort B. Six-mo PFS for CERT was 60.8% (95% CI 44.1%, 73.9%) and for PLA was 25% (95% CI 9.1%, 44.9%). mPFS was 7.5 mo for CERT & 4.7 mo for PLA (HR 0.60 95% CI 0.34, 1.07, p=0.08). ORR was 45.2% for CERT & 19% for PLA. Overall disease control rate was 85.9% for CERT & 61.9% for PLA. Preliminary median OS was 10.3 mo with CERT and 9.2 mo with PLA. Consistent with prior reports for GEM/NPC, grade 3/4/5 adverse events occurred in 88% of subjects in the CERT arm and 77% in the PLA arm. Grade 3/4 haematologic toxicity for CERT v PLA: Neutropenia 34.3% and 28.6%, thrombocytopenia 19% and 14.3%. Conclusion(s): Double-dose CERT + GEM/NPC demonstrated trends for a clinically meaningful PFS and ORR improvements in mPDAC, with a manageable safety profile. The 6-mo PFS rate (60.8%) supports further investigation of CERT as a novel therapeutic agent in mPDAC. Clinical trial identification: ACTRN12621001290886 (ANZ). 24 Sept 2021. Legal entity responsible for the study: Australasian Gastro-Intestinal Trials Group. Funding(s): Lisata Therapeutics. Disclosure: A. Dean: Financial Interests, Personal, Leadership Role, Director Shareholder: Valo Therapeutics; Financial Interests, Personal, Speaker's Bureau: Juniper Biologics. K. Sjoquist: Financial Interests, Institutional, Research Grant: Bayer, Lisata, Amgen; Financial Interests, Personal, Speaker's Bureau: MSD; Financial Interests, Personal, Other, Travel Grant: Astellas; Financial Interests, Personal, Advisory Board: BMS, Servier. K.K. Buck: Financial Interests, Institutional, Other, Chief Medical Officer and Head of Research and Development: Lisata Therapeutics; Financial Interests, Institutional, Full or part-time Employment, Chief Medical Officer and Head of Research and Development: Lisata Therapeutics; Financial Interests, Institutional, Stocks/Shares, Chief Medical Officer and Head of Research and Development: Lisata Therapeutics. All other authors have declared no conflicts of interest.Copyright © 2025