Certepetide Displays Positive Efficacy Trend in Metastatic PDAC

Data from cohort B revealed that a 6-month PFS benefit was observed in the investigational arm, with rates of 60.8% and 25.0% in the certepetide and placebo groups, respectively.

The addition of certepetide (CEND-1) to standard-of-care (SOC) chemotherapy displayed a positive efficacy trend, including improved progression-free survival (PFS) and objective response rate (ORR), vs placebo/chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to a news release on preliminary results from cohort B of the phase 2b ASCEND study (NCT05042128).

According to developers from The Australasian Gastro-Intestinal Trials Group (AGITG), the National Health and Medical Research Council (NHMRC) Clinical Trials Center, and Lisata Therapeutics Inc, results from the phase 2b trial are scheduled to be presented at the upcoming European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress on July 2, 2025.

Data from cohort B revealed that a 6-month PFS benefit was observed in the investigational arm, with rates of 60.8% and 25.0% in the certepetide and placebo groups, respectively. Additionally, the median PFS in each respective group was 7.5 months and 4.7 months. Furthermore, ORR favored certepetide, with rates of 45.2% vs 19.0% with placebo, and a median overall survival (OS) of 10.32 months vs 9.23 months.

Preliminary data from cohort A of the trial were presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Symposium.2 Data from the trial revealed that among 66 patients treated with certepetide and 29 patients treated with placebo, the respective 6-month PFS rates were 49.0% (95% CI, 36.4%-60.5%) vs 40.8% (95% CI, 22.6%-58.3%), and the median PFS was 5.5 months in each arm. Furthermore, the ORR in the respective groups was 38.3% vs 26.9%, with 4 complete responses observed in the certepetide group.

A comparison of the cross-cohort data revealed that the addition of 2 doses of the investigational agent in cohort B to SOC chemotherapy displayed a clinically meaningful PFS and ORR improvement in patients with metastatic PDAC. Final data from both cohorts of the ASCEND study are anticipated to be available later in 2025.

“The data from [the phase 2b] ASCEND [trial] provides us with critical new knowledge that will significantly enhance our understanding of how to optimally treat patients [with] pancreatic cancer,” Andrew Dean, MBChB, MRCP (UK), FRACP, medical oncologist, head of the Department of Medical Oncology at St. John of God Subiaco Hospital, and ASCEND study chair, said in the news release.1 “We are excited by the evidence of certepetide’s therapeutic effect and encourage the continued development of this potentially treatment paradigm-changing compound.”

The phase 2b ASCEND trial randomly assigned 158 patients with metastatic PDAC to receive SOC chemotherapy with nab-paclitaxel and gemcitabine with certepetide or placebo. The study was composed of 2 sequentially enrolled dosing regimens, with cohort A employing 3.2 mg/kg of certepetide or matching placebo intravenously over 1 minute following gemcitabine infusion but before nab-paclitaxel infusion. Cohort B included the same dosing regimen, but with an additional dose of certepetide or placebo 4 hours following the initial dose.

Patients in both arms received 125 mg/m2 of nab-paclitaxel and 1000 mg/m2 of gemcitabine on days 1, 8, and 15 of 28-day cycles.3

The primary end point of the study was PFS. Secondary end points included OS, ORR, patient-reported outcomes, and safety.

Patients 18 years and older with measurable metastatic PDAC per RECIST v 1.1 criteria were eligible for enrollment. Additional eligibility criteria included being able to provide archival tumor tissue, an ECOG performance score of 0 or 1, adequate renal and hematologic function, and adequate hepatic function.

“We are pleased with the promising cohort B data of the ASCEND trial. These data, taken with those previously reported for cohort A, reinforce our confidence in the therapeutic promise of certepetide,” David J. Mazzo, PhD, president and chief executive officer of Lisata, stated in the news release.1 “Along with its attractive safety profile, we continue to believe that certepetide has the potential to transform the treatment landscape for [metastatic] PDAC and many other devastating solid tumors.”

References

1. Positive preliminary cohort B results from the AGITG-led ASCEND trial to be presented at ESMO GI evaluating Lisata’s certepetide in combination with standard-of-care chemotherapy in metastatic pancreatic cancer. News release. AGITG, NHMRC Clinical Trials Centre, Lisata Therapeutics, Inc. June 26, 2025. Accessed June 27, 2025. https://tinyurl.com/4eeu96cy
2. Dean AP, Sjoquist K, Gebski V, et al. 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. J Clin Oncol. 2025;23(suppl 4):728. doi:10.1200/JCO.2025.43.4_suppl.728
3. The ASCEND study: gemcitabine and nab-paclitaxel with LSTA1 (certepetide) or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma (ASCEND). ClinicalTrials.gov. Updated October 22, 2024. Accessed June 27, 2025. https://tinyurl.com/juspw8nw