Certepetide/FOLFIRINOX Displays Encouraging Preliminary Feasibility in PDAC

Preliminary data from the pancreatic ductal adenocarcinoma (PDAC) cohort of the phase 1/2a CENDIFOX trial (NCT05121038) revealed that the addition of certepetide (CEND-1) to leucovorin (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX) produced promising preliminary results for patients with resectable or borderline resectable disease, according to a news release from the drug’s developer, Lisata Therapeutics.¹

Specifically, the combination displayed safety and feasibility among this patient population, with no serious adverse effects (SAEs) attributable to the investigational agent. Moreover, 10 of 35 patients enrolled in the PDAC cohort completed protocol-prescribed pre-surgical courses of therapy and were eligible to undergo resection for their cancer. Among these patients, the R0 resection rate was 50%, with 70% experiencing a pathologic partial response.

Further data revealed that the 2-year overall survival (OS) rate was 60%, and the median disease-free survival (DFS) at 2 years was 12 months. Moreover, enhanced immune cell infiltration was exhibited in an analysis of the tumor tissue, and an increased expression of immune markers including CD68, PD-1, and PD-L1 was observed. Finally, the developers suggested that this combination may help transform pancreatic tumors into “immune-hot” lesions, which would make immunotherapies more effective in treating the disease.

“The preliminary trial data have been [quite] promising, and we are excited to share these findings with the broader oncology community,” lead investigator Anup Kasi, MD, MPH, associate professor of Medical Oncology at The University of Kansas (KU) Medical Center, stated in the news release on the study findings.¹ “The ability of certepetide to improve drug delivery and influence the tumor microenvironment may offer a potential new and exciting treatment approach for pancreatic cancer. We are optimistic studies like CENDIFOX will pave the way for more effective combination therapies for difficult-to-treat solid tumor cancers.”

The full preliminary data from the phase 1/2a CENDIFOX trial will be presented at the American Association for Cancer Research (AACR) Special Conference in Cancer Research: Advances in Pancreatic Cancer Research. Kasi will present poster A070 titled “CENDIFOX: Phase I/II Trial of CEND-1 (LSTA1, certepetide) with Neoadjuvant mFOLFIRINOX in Resectable and Borderline Resectable PDAC,” in the Emerging Science Driving Transformative Solutions session on September 29, 2025.

Patients in the pancreatic cohort of the trial initially underwent a biopsy for tissue immune profile in the absence of archived tissue.² FOLFIRINOX was given via infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Furthermore, the certepetide/FOLFIRNOX combination was given via infusion for 3 cycles, with surgery occurring 72 hours following the final infusion.

The primary end point of the trial was incidence of AEs per CTCAE v5.0 criteria. Secondary end points included OS, DFS, overall response rate, R0 resection rate, and pathological response rate.

Those with an ECOG performance status of 0 or 1, 1 or more evaluable lesions, histologically confirmed resectable or borderline resectable disease, a life expectancy of 3 or more months, and those with adequate archival tissue from prior biopsy or willingness to undergo biopsy were eligible for enrollment in the PDAC cohort.

“We believe these findings are a significant step forward in a disease with few beneficial treatment options. By improving drug delivery and modulating the tumor microenvironment to re-engage the immune system, we see a path forward for this program and the potential to change the outlook for patients,” Kristen K. Buck, MD, executive vice president of Research and Development and Chief Medical Officer at Lisata, expressed in the news release.¹

References

1. Lisata Therapeutics announces encouraging preliminary results from the pancreatic cancer cohort of the CENDIFOX trial. News release. Lisata Therapeutics. September 29, 2025. Accessed September 29, 2025.https://tinyurl.com/47fuj4d7
2. CEND-1 in combination with neoadjuvant FOLFIRINOX with or without panitumumab (CENDIFOX). ClinicalTrials.gov. Updated December 17, 2024. Accessed September 29, 2025. https://tinyurl.com/y8dzm2fs