FDA Grants Orphan Drug Designation to LSTA1 in Osteosarcoma


LSTA1 has been granted orphan drug designation by the FDA for the treatment of patients with osteosarcoma.

Kristen K. Buck, MD

Kristen K. Buck, MD

The FDA has granted orphan drug designation to the investigational agent LSTA1 (CEND-1) for the treatment of pediatric or adult patients with osteosarcoma.1

This announcement follows the FDA’s decision to grant rare pediatric disease designation to LSTA1 in osteosarcoma on March 21, 2024.2

LSTA1 leverages a novel uptake pathway within tumor cells, allowing covalently bound anticancer agents to more effectively penetrate solid tumors and accumulate within the tumor environment. This mechanism is achieved through the binding of LSTA1 to alpha-v integrins, which are selectively expressed in tumors but not in healthy tissues.3 Following binding, LSTA1 is cleaved by proteases, forming a CendR fragment that then binds to neuropilin-1, initiating and activating the uptake pathway within the tumor cells. This targeted process allows for enhanced tumor cell penetration and accumulation of the agent, contributing to its effectiveness in solid tumors.

“We are thrilled to have received another favorable regulatory designation from the FDA. This underscores the significant unmet medical need and demand for better treatments for patients diagnosed with osteosarcoma,” Kristen K. Buck, MD, executive vice president of Research and Development and chief medical officer of Lisata Therapeutics, stated in a news release.1 “Osteosarcoma, while rare, is a type of bone cancer that is often associated with high morbidity, early metastasis, rapid progression, and poor prognosis. Receiving an orphan drug designation from the FDA is an important milestone as we plan for future clinical expansion of LSTA1, and we believe it reflects the broad clinical utility of LSTA1 for the treatment of a wide array of solid tumors.”

LSTA1 has been shown to bolster the delivery of chemotherapeutics, immunotherapies, and RNA-based agents through nonclinical data.2,3 Moreover, preclinical models indicate that LSTA1 may modulate the tumor microenvironment, thereby enhancing immune responses. In clinical trials aiming to improve chemotherapy delivery within pancreatic cancer, LSTA1 also demonstrated favorable safety, tolerability, and activity.

LSTA1 was granted orphan drug designation by the FDA in August 2023, for use as a potential therapeutic option in patients with malignant glioma.4 The agent was also granted orphan drug designation for pancreatic cancerby the European Medicines Agency’s Committee for Orphan Medical Products in October 20235 and fast track designation from the FDA in this disease setting.1

Investigations of LSTA1-based combination regimens are being conducted in patients with solid tumors including metastatic pancreatic ductal adenocarcinoma (mPDAC), colon cancer, appendiceal cancer, and glioblastoma multiforme.6

In the phase 2 ASCEND trial (NCT05042128), LSTA1 plus gemcitabine and nab-paclitaxel (Abraxane) is being compared with placebo plus gemcitabine and nab-paclitaxel in patients with previously untreated mPDAC.7 Patients will receive nab-paclitaxel at 125 mg/m2 plus gemcitabine at 1000mg/m2 and either intravenous LSTA1 at 3.2 mg/kg or placebo on days 1, 8, and 15 of each 28-day cycle.8 Progression-free survival will serve as the primary end point of the ASCEND. Key secondary end points will include overall survival, objective tumor response rate, patient-reported outcomes, and the incidence of treatment-emergent adverse effects.

Additionally, the phase 1b/2 CENDIFOX trial (NCT05121038), which is being conducted in the United States, 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

Lastly, the ongoing phase 2 BOLSTER study (NCT05712356) is evaluating the safety, tolerability, and efficacy of LSTA1 plus standard-of-care (SOC) therapy vs SOC alone in patients with advanced head and neck squamous cell carcinoma, cholangiocarcinoma, and other solid tumors.7


  1. 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 April 10, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-us-fda-orphan-drug-designation-0
  2. Lisata Therapeutics Announces U.S. FDA rare pediatric disease designation granted to LSTA1 for the treatment of osteosarcoma. News release. Lisata Therapeutics, Inc. March 21, 2024. Accessed April 10, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-us-fda-rare-pediatric-disease
  3. Advanced solid tumors – LSTA1. Lisata Therapeutics, Inc. website. Accessed April 10, 2024. https://www.lisata.com/product-development-pipeline/pancreatic-cancer-advanced-solid-tumors-lsta1/
  4. Lisata Therapeutics announces U.S. FDA orphan drug designation granted to LSTA1 for the treatment of malignant glioma. News release. Lisata Therapeutics, Inc. August 8, 2023. Accessed April 10, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-us-fda-orphan-drug-designation
  5. 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 April 10, 2024. https://ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-european-medicines-agency-has
  6. Our product development pipeline. Lisata Therapeutics, Inc. website. Accessed April 10, 2024. https://www.lisata.com/product-development-pipeline/
  7. Clinical trials. Lisata Therapeutics, Inc. website. Accessed April 10, 2024. https://www.lisata.com/active-clinical-trials/
  8. The ASCEND study: gemcitabine and nab-paclitaxel with CEND-1 or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma (ASCEND). ClinicalTrials.gov. Updated December 21, 2023. Accessed April 10, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05042128
  9. CEND-1 in combination with neoadjuvant FOLFIRINOX with or without panitumumab (CENDIFOX). ClinicalTrials.gov. Updated November 24, 2021. Accessed April 10, 2024. https://www.clinicaltrials.gov/study/NCT05121038
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