Lisata Therapeutics and WARPNINE have successfully completed patient enrollment in the Phase 1b/2a iLSTA trial evaluating certepetide in combination with standard-of-care chemotherapy and immunotherapy for locally advanced non-resectable pancreatic ductal adenocarcinoma (PDAC). The study, conducted at St John of God Subiaco Hospital in Western Australia, demonstrated encouraging preliminary efficacy results with a 60% overall response rate and 100% disease control rate.
Trial Design and Patient Population
The randomized, single-blind, single-center trial enrolled 30 patients with locally advanced, unresectable PDAC divided into three treatment cohorts in a 1:1:4 ratio. Cohort 1 (n=5) received standard-of-care chemotherapy with placebo durvalumab and placebo certepetide. Cohort 2 (n=5) received standard-of-care chemotherapy plus certepetide and placebo durvalumab. Cohort 3 (n=20) received standard-of-care chemotherapy plus durvalumab and certepetide.
The study evaluated certepetide in combination with nab-paclitaxel and gemcitabine chemotherapy plus durvalumab immunotherapy, compared to standard-of-care alone. This represents the first study evaluating certepetide in locally advanced non-resectable PDAC, an earlier stage in the disease process than metastatic PDAC.
Efficacy Results
Updated preliminary data presented at the 2025 ESMO Gastrointestinal Cancers Congress on July 3, 2025, showed significant clinical activity. After 4 treatment cycles, 13 of 20 participants demonstrated a RECIST partial response, with 11 patients in Cohort 3. One participant in Cohort 2 exhibited a RECIST complete response. The remaining 6 participants demonstrated stable disease with less than 22.0% decrease in tumor size. Notably, no participant showed an increase in tumor size.
Biomarker analysis revealed that 16 of 20 participants experienced a decrease in CA19-9 levels. Seven participants showed a greater than 90% reduction in CA19-9 levels, with 5 patients in Cohort 3, while 9 participants showed a greater than 50% reduction in CA19-9 levels, with 6 patients in Cohort 3.
Mechanism of Action and Regulatory Status
Certepetide (formerly LSTA1) is an internalizing RGD (arginyl-glycyl-aspartic acid or iRGD) cyclic peptide designed to activate a novel uptake pathway that allows co-administered or tethered anti-cancer drugs to target and penetrate solid tumors more effectively. The drug actuates this active transport system in a tumor-specific manner, resulting in systemically co-administered anti-cancer drugs more efficiently penetrating and accumulating in the tumor.
The compound has also been shown to modify the tumor microenvironment, resulting in tumors that are more susceptible to immunotherapies. Certepetide has received Fast Track designation and Orphan Drug Designation for pancreatic cancer in both the U.S. and E.U., as well as Orphan Drug Designation for glioma and osteosarcoma in the U.S. Additionally, it has received Rare Pediatric Disease Designation for osteosarcoma in the U.S.
Clinical Significance
"It is especially important to note that this is the first study in which we are evaluating locally advanced non-resectable PDAC, an earlier stage in the disease process than metastatic PDAC. Immunotherapy has largely been ineffective in this patient population, and thus, we were encouraged by the preliminary data," stated Kristen K. Buck, M.D., Executive Vice President of Research and Development and Chief Medical Officer of Lisata.
Meg Croucher, Chief Executive Officer of WARPNINE, emphasized the potential impact: "Given the highly promising preliminary data presented at ESMO-GI, which highlighted a 60% overall response rate and 100% overall disease control rate, we are even more optimistic about the potential impact of this therapy."
Study Collaboration
The collaboration brought together drug supply and clinical strategy from Lisata, drug supply from AstraZeneca, and operational execution and funding support from WARPNINE. St John of God Subiaco Hospital, founded in 1898, is one of the leading private hospitals in Australia with one of the busiest clinical trial units in the country, currently conducting 58 open trials.
WARPNINE, Western Australia's first not-for-profit clinical research organization for pancreatic, gastro-intestinal and rare cancers, was established by leading cancer specialists to address inequity in cancer outcomes for underfunded and under-researched malignancies.
