ASCEND: A randomised, double-blinded, phase II study of gemcitabine and nab‐paclitaxel with CEND‐1/LSTA1 or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma

Research Funding
Pharmaceutical/Biotech Company
Lisata Therapeutics, Inc

Background:
LSTA1 is a novel cyclic peptide with high tumor vascular endothelium specificity that activates an endocytotic/exocytotic transport pathway on stroma and tumor. LSTA1 potentiates greater intratumoral access for co-administered or tethered anti-cancer agents, including small molecules, antibodies, and nanoparticles, leading to increased anti-neoplastic activity. Preclinical studies in solid tumor models have shown co-administrating LSTA1 is effective in augmenting the delivery and activity of multiple anti-cancer agents. LSTA1 has been evaluated in 31 patients in a Phase I study in metastatic pancreatic ductal adenocarcinoma (mPDAC) demonstrating an objective response in 59% of patients, a 79% disease control rate at 16 weeks with a median progression free survival (PFS) of ~9.9 months. No dose limiting toxicities were observed. The ASCEND study will determine whether LSTA1 when added to SOC chemotherapy is active and safe as first-line treatment of mPDAC, and whether an additional dose of LSTA1 administered approximately 4 hours after chemotherapy further improves anti-cancer activity.

Methods:
ASCEND is a randomized, double-blind, placebo-controlled phase II trial evaluating the safety and efficacy of LSTA1 3.2 mg/kg in combination with standard of care chemotherapy (nab-paclitaxel 125mg/m2 and gemcitabine 1000mg/m2 on days 1, 8, and 15, every 28 days) in patients with histologically proven, previously untreated mPDAC. A total of 155 subjects will be randomized 2:1 in favor of study intervention in two cohorts and stratified by age, ECOG status, presence of liver metastasis, and study site. Patients in cohort A receive single doses of LSTA1 or placebo, and for cohort B, two doses of LSTA1 or placebo spaced 4 hours apart. Tumour assessment occurs every 8-weeks from randomization until disease progression or commencement of a new anti-cancer therapy. The primary endpoint is PFS. Secondary endpoints include objective tumour response safety, overall survival, and patient reported outcomes. At 14 Feb 2023, 70 participants have been enrolled from Australian sites. Sites in Ireland and New Zealand are anticipated to open this year. Clinical trial information: NCT05042128.