FDA Grants Orphan Drug Designation to Certepetide in Cholangiocarcinoma
The FDA has granted an orphan drug designation (ODD) to the investigational agent certepetide (formerly LSTA1) for the treatment of cholangiocarcinoma, according to an announcement from Lisata Therapeutics, Inc. The agent is currently being evaluated alongside standard-of-care (SOC) therapies for patients with first- and second-line cholangiocarcinoma in the phase 2 BOLSTER trial (NCT05712356).
“Cholangiocarcinoma is a rare and aggressive form of cancer that presents a significant challenge for patients due to limited treatment options, especially after initial therapy,” Kristen K. Buck, MD, executive vice president of Research and Development and chief medical officer of Lisata, stated in the news release. “Receiving ODD for our investigational product, certepetide, is a pivotal step toward addressing the unmet need for cholangiocarcinoma therapies and providing patients with new, innovative treatment options.”
Certepetide is a cyclic peptide designed to activate the C-end rule active transport mechanism within tumor cells to enhance the penetration and accumulation of covalently bound anticancer agents in solid tumors. Preclinical data have shown that certepetide enhances the delivery of chemotherapies, immunotherapies, and RNA-based agents as well as modulates the tumor microenvironment to boost immune responses. Notably, in clinical trials, both completed and ongoing, the addition of certepetide has demonstrated favorable safety, tolerability, and improvements to chemotherapy activity.
BOLSTER is a double-blind, placebo-controlled, multi-center, randomized study evaluating the addition of certepetide to gemcitabine, cisplatin and durvalumab (Imfinzi) vs the SOC alone in patients with cholangiocarcinoma and other solid tumors being treated in the first- and second-line.
Patients in the first-line cohort will receive 1500 mg of intravenous (IV) durvalumab every 21 days plus 25 mg/m² of IV cisplatin and 1000 mg/m² of IV gemcitabine on day 1 and 8 every 21 days for 8 cycles, then every 28 days for additional cycles. In the second-line cohort, patients will receive FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) every 14 days. These respective regimens will be administered alongside either placebo or 3.2 mg/kg of IV certepetide as a slow push over 1 minute. The study’s primary end point is the incidence of adverse effects.
Previously, certepetide was granted ODD by the FDA for use as a potential therapeutic option in patients with malignant glioma in August 2023; rare pediatric disease designation in osteosarcoma in March, 2024; and ODD for osteosarcoma in April 2024. Additionally, the agent received orphan drug designation for pancreatic cancer by the European Medicines Agency’s Committee for Orphan Medical Products in October 2023, and fast track designation from the FDA in this disease setting.
