AGITG ASCEND: Randomised, double-blind phase II study of certepetide or placebo added to gemcitabine plus nab-paclitaxel in patients with untreated metastatic pancreatic ductal adenocarcinoma: Initial results.

728 Background: Gemcitabine (GEM) plus nab-paclitaxel (NAB-PAC) is a standard first-line chemotherapy regimen for advanced/metastatic pancreatic ductal adenocarcinoma (PDAC), with median Progression Free Survival (mPFS) and Overall Survival (mOS) of 5.5 & 8.7 in the MPACT trial and 5.6 & 9.2 months (mo) in the NAPOLI 3 trial, respectively. Certepetide (formerly LSTA1 or CEND-1) is a novel cyclic peptide that improves targeted penetration of co-administered drugs into tumor and stroma, leading to potentially increased anti-neoplastic activity. ASCEND is a randomized phase II trial designed to investigate the impact of adding certepetide to GEM/NAB-PAC. (NCT05042128). Methods: Eligible participants (pts) with histologically confirmed advanced PDAC and ECOG 0-1 were randomized 2:1 to receive GEM/NAB-PAC plus certepetide (3.2 mg/kg) or placebo (PLA) on days 1, 8, & 15 of a 28-day cycle. Stratification was by age (<65/≥65 years), ECOG (0/1), presence of liver metastasis (Y/N) and trial site. The primary objective was to determine the effect of adding certepetide to GEM/NAB-PAC on PFS. Objective tumor response rate (OTRR), safety and OS were secondary objectives. This non-comparative phase II design targeted a PFS increase of 17% at 6 mo from 47% to 63%. A sample size of 65 patients in the certepetide arm was expected to have 80% power, with 95% confidence to exclude an uninteresting 6-mo PFS rate of 47%. Results: 95 pts (66 certepetide, 29 PLA) were enrolled between May 2022 to December 2023. 6-mo PFS in the certepetide and PLA groups was 49.0% (95% CI 36.4%, 60.5%) and 40.8 (95% CI 22.6%, 58.3%) respectively, with mPFS of 5.5 mo in both groups. mOS was 12.42 mo for the certepetide and 9.72 mo for the PLA. An OTRR of 38.3% (certepetide) and 26.9% (PLA) was observed. Of note, 4 complete responses were observed in the certepetide group vs. 0 in PLA group. In subjects with ECOG 0, 6 mo PFS was 68.1% (95% CI 48.7%, 81.4%) in the certepetide compared to 36.4% (95% CI 11.2%, 62.7%) in the PLA. Grade ≥3 toxicities were similar in both groups at 16% (certepetide) and 15% (PLA). Conclusions: The addition of certepetide is safe and despite showing no improvement in 6-mo PFS, a possible signal of benefit in OS and OTRR, including the 4 complete responses was observed, warranting further investigation. A further cohort of the ASCEND study evaluating the addition of a second dose of certepetide is ongoing. Clinical trial information: NCT05042128 .