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Certepetide plus gemcitabine and nab-paclitaxel was safe and effective in patients with untreated metastatic pancreatic ductal adenocarcinoma.
Certepetide Plus Chemotherapy in Metastatic PDAC
| Image by Ashling Wahner & MJH Life Sciences Using AI
Promising efficacy trends were observed with the addition of certepetide (LSTA1) to gemcitabine plus nab-paclitaxel (Abraxane) in patients with treatment-naive metastatic pancreatic ductal adenocarcinoma (PDAC), according to data from the phase 2 AAGITG ASCEND trial (NCT05042128) presented during the 2025 ESMO Gastrointestinal Cancers Congress.1
Patients in cohort B who received certepetide in combination with chemotherapy in the intention-to-treat population (n = 42) achieved a median progression-free survival (PFS) of 7.5 months vs 4.7 months in patients who received placebo in place of certepetide (n = 21; HR, 0.60; 95% CI, 0.34-1.07; log-rank P = .08). The 6-month PFS rates were 60.8% (95% CI, 44.1%-73.9%) and 25% (95% CI, 9.1%-44.9%), respectively.
The overall response rate (ORR) in the certepetide arm was 45.2% compared with 19% in the placebo arm. The disease control rates (DCRs) were 85.7% and 61.9%, respectively. Notably, 5 patients in the investigational arm achieved a complete response (CR).
“Promising trends in PFS and ORR with double-dose certepetide added to standard gemcitabine and nab-paclitaxel [were observed],” Andrew Dean, MBChB, MRCP, FRACP, said during the presentation. “The 6-month PFS rate of 60.8% together with the 5 patients who obtained a CR on treatment support further investigation of certepetide as a novel therapeutic agent in metastatic PDAC.”
Dean is the head of the Department of Medical Oncology at St John of God Subiaco Hospital in Australia.
AAGITG ASCEND enrolled adult patients with metastatic PDAC who were suitable for frontline treatment with gemcitabine plus nab-paclitaxel. Eligible patients also needed to have measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1. Patients were stratified by age (65 years vs > 65 years), ECOG performance status (0 vs 1), presence of liver metastases (yes vs no), and disease site location.
In cohort B, patients were randomly assigned 2:1 to receive intravenous (IV) certepetide at 3.2 mg/kg2 followed by another dose 4 hours later, or placebo. Patients in both arms received IV nab-paclitaxel and gemcitabine at 125 mg/m2 and 1000 mg/m2, respectively. Treatment in both arms was administered on days 1, 8, and 15 of each 28-day cycle. The minimum follow-up duration was 18 months.
The primary end point was PFS.2 Secondary end points included overall survival (OS), ORR, patient-reported outcomes, and safety.
At baseline, the median age in the overall population (n = 63) was 63 years (range, 21-78).1 Most patients were female (51%), had an ECOG performance status of 1 (59%), had adenocarcinoma (87%), had stage IV disease (94%), and had liver metastases (78%). Pancreatic tumor locations consisted of the body (29%), head (49%), neck (2%), or tail (21%).
Preliminary survival data showed that the median OS in the investigational arm was 10.3 months compared with 9.2 months in the placebo arm. The addition of certepetide to chemotherapy resulted in a 14% decrease in the risk of death compared with placebo (HR, 0.86; 95% CI, 0.46-1.61; log-rank P = .64).
Regarding safety, grade 3 or higher adverse effects (AEs) were reported in 88% and 77% of patients in the investigational and placebo arms, respectively. Grade 3 or 4 hematologic toxicities that occurred in these respective arms included neutropenia (34.3% vs 28.6%) and thrombocytopenia (19% vs 14.3%).
Common grade 3 or higher AEs in the certepetide arm included decreased neutrophil count (33%), anemia (21%), and decreased platelet count (19%). In the placebo arm, common grade 3 or higher AEs included decreased neutrophil count (29%), peripheral sensory neuropathy (10%), febrile neutropenia (10%), lung infection (10%), and increased alanine aminotransferase levels (10%).
“The toxicities were as expected and were easily manageable,” Dean noted.
Disclosures: Dean had no relevant financial relationships to disclose.
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