ASCEND Trial of Certepetide Plus Chemo Fails to Improve PFS in Metastatic PDAC
Certepetide plus chemotherapy showed signs of efficacy but failed to improve progression-free survival in metastatic PDAC in the ASCEND trial.
Pancreatic cancer, 3D rendering: © matthieu - stock.adobe.com
Data from the phase 2 ASCEND trial (NCT05042128) showed that adding the novel cyclic peptide certepetide to gemcitabine and nab-paclitaxel (Abraxane) demonstrated signs of efficacy but did not improve progression-free survival (PFS) compared with chemotherapy alone in patients with untreated metastatic pancreatic ductal adenocarcinoma (PDAC). Findings were presented at the 2025 Gastrointestinal Cancers Symposium.
Results revealed that the 6-month PFS rate was 49.0% (95% CI, 36.4%-60.5%) in the investigational arm vs 40.8% (95% CI, 22.6%-58.3%) in the control arm, with a median PFS of 5.5 months in both arms (HR, 0.96; 95% CI, 0.60-1.53; log-rank P = .85). The median overall survival (OS) was 12.42 months in the investigational arm vs 9.72 months in the control arm (HR, 0.95; 95% CI, 0.56-1.60; log-rank P = .82). The objective tumor response rates (OTRRs) were 38.3% and 26.9% for the investigational and control arms, respectively.
“The addition of certepetide is safe and despite showing no improvement in 6-month PFS, a possible signal of benefit in OS and ORR (including 4 complete responses) was observed, warranting further investigation,” lead study author Andrew Dean, MBChB, MRCP (UK), FRACP, head of the Department of Medical Oncology at St John of God Subiaco Hospital, and a consultant at GenesisCare at Shenton House in Perth, Australia, and coauthors, wrote in the poster. “A further cohort (cohort B) of the ASCEND study evaluating the addition of a second dose of certepetide is ongoing.”
Gemcitabine plus nab-paclitaxel is a standard frontline therapy for patients with advanced and metastatic PDAC. Certepetide is a novel cyclic peptide that enhances the penetration of concurrently administered drugs into the tumor and stroma, resulting in potentially increased antineoplastic activity.
The randomized, double-blind, multicenter ASCEND was designed to evaluate the impact of adding certepetide to this chemotherapy backbone in this population.
Eligible patients had histologically confirmed advanced PDAC suitable for therapy with gemcitabine and nab-paclitaxel. Patients were also required to have measurable disease per RECIST 1.1 and an ECOG performance status of 0 or 1. Patients were randomly assigned 1:1 to 3.2 mg/kg of certepetide (n = 65) or placebo (n = 30) on days 1, 8, and 15 of a 28-day cycle, both in combination with 1,000 mg/m2 of intravenous (IV) gemcitabine and 125 mg/m2 of IV nab-paclitaxel.
Patients underwent a minimum 18-month follow-up period, during which data were evaluated for PFS, OTRR, OS, safety, patient-reported outcomes (PROs), exploratory research biomarkers, and E-PRO feasibility.
A total of 198 patients were screened; 66 patients were allocated to the investigational arm and 29 were allocated to the placebo arm between May 2022 and December 2023. One patient from each arm did not receive the allocated intervention and were omitted from the full analysis set.
The primary analysis was conducted with 70 total deaths.
Baseline characteristics in the overall population (n = 95) indicated that the mean age was 65 years (range, 37-86) and most patients were male (60%) and had an ECOG performance status of 1 (54%). The pancreatic tumor location was found in the body (19%), head (44%), and tail (31%), and was unknown in 6.3% of cases. Adenocarcinoma represented the most common histologic subtype (89%) followed by poorly differentiated carcinoma (11%). Most patients had stage IV disease (96%) as opposed to stage III disease (4%) according to the 8th edition of the AJCC. Sites of metastatic disease included the liver (73%), pulmonary tract (28%), peritoneum (21%), and other (28%). Prior treatment included systemic therapy (15%) and surgery (19%).
Additional findings indicated that among patients with an ECOG performance status of 0, the 6-month PFS rate was 68.1% (95% CI, 48.7%-81.4%) in the investigational arm vs 36.4% (95% CI, 11.2%-62.7%) in the control arm.
In terms of safety, grade 3/4 adverse effects (AEs) that occurred in at least 10% of patients included decreased neutrophil count (investigational: 18% vs control: 8%), anemia (14%; 4%), decreased platelet count (12%; 4%), peripheral sensory neuropathy (9%; 4%), febrile neutropenia (8%; 3%), lung infection (8%; 3%), fatigue (6%; 3%), sepsis (6%; 3%), thromboembolic event (6%; 2%), and increased alanine aminotransferase levels (5%; 2%).
