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.¹

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.^1,2 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 Trial Design

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.^1,3 Patients are required to have confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma that has not been treated with prior systemic chemotherapy, targeted therapy, or loco-regional therapy; and no disease progression after first-line chemotherapy and immunotherapy. Notably, patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible. An ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and 1 or more measurable lesions per RECIST 1.1 criteria are also necessary for study inclusion.

Following early completion of enrollment onto the trial in July of 2024, the Company added another arm to the BOLSTER trial evaluating the agent in the second line. Enrollment for this cohort is expected to begin in late 2024.⁴

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.³

Evaluation of Certepetide Continues in Other Tumor Types

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.^5-7 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.^1,8

Investigations of LSTA1 combination regimens are being conducted in solid tumors including metastatic pancreatic ductal adenocarcinoma (PDAC), pancreatic cancer, colon cancer, appendiceal cancer, and glioblastoma multiforme.²

These include the phase 2 ASCEND trial (NCT05042128) evaluating certepetide plus gemcitabine and nab-paclitaxel in patients with previously untreated metastatic PDAC; and the phase 1b/2 CENDIFOX trial (NCT05121038), which is being conducted in the United States and will assess LSTA1 plus neoadjuvant FOLFIRINOX (leucovorin, 5-fluorouracil, and irinotecan) with or without panitumumab (Vectibix) in patients with pancreatic, colon, and appendiceal cancers.⁹

References

1. Lisata Therapeutics’ certepetide granted FDA orphan drug designation for the treatment of cholangiocarcinoma. News Release. Lisata Therapeutics, Inc. September 5, 2024. Accessed September 5, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-certepetide-granted-fda-orphan-drug
2. Advanced solid tumors – LSTA1. Lisata Therapeutics, Inc. website. Accessed September 5, 2024.https://www.lisata.com/product-development-pipeline/pancreatic-cancer-advanced-solid-tumors-certepetide/
3. A study of LSTA1 when added to standard of care versus standard of care alone in patients with advanced solid tumors (BOLSTER). ClinicalTrials.gov. Updated September 3, 2024. Accessed September 5, 2034. https://clinicaltrials.gov/study/NCT05712356
4. Lisata Therapeutics announces completion of enrollment in its phase 2a BOLSTER trial of certepetide in first-line cholangiocarcinoma. News Release. Lisata Therapeutics, Inc. July 16, 2024. Accessed September 5, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-completion-enrollment-its-phase-2a
5. Lisata Therapeutics announces US FDA orphan drug designation granted to LSTA1 for the treatment of malignant glioma. News release. Lisata Therapeutics, Inc. August 8, 2023. Accessed September 5, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-us-fda-orphan-drug-designation
6. Lisata Therapeutics Announces US FDA rare pediatric disease designation granted to LSTA1 for the treatment of osteosarcoma. News release. Lisata Therapeutics, Inc. March 21, 2024. Accessed September 5, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-us-fda-rare-pediatric-disease
7. Lisata Therapeutics announces U.S. FDA orphan drug designation granted to LSTA1 for the treatment of osteosarcoma. News release. Lisata Therapeutics, Inc. April 9, 2024. Accessed September 5, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-us-fda-orphan-drug-designation-0
8. Lisata Therapeutics announces European Medicines Agency has granted LSTA1 orphan drug designation for the treatment of pancreatic cancer. News release. Lisata Therapeutics. October 17, 2023. Accessed September 5, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-european-medicines-agency-has
9. Product development pipeline. Lisata Therapeutics, Inc. website. Accessed September 5, 2024. https://www.lisata.com/product-development-pipeline/