FDA Awards Orphan Drug Designation to LSTA1 for Malignant Glioma

August 8, 2023

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The FDA has granted orphan drug designation to LSTA1 for use as a potential therapeutic option in patients with malignant glioma, according to an announcement from Lisata Therapeutics, Inc.

FDA

The FDA has granted orphan drug designation to LSTA1 (CEND-1) for use as a potential therapeutic option in patients with malignant glioma, according to an announcement from Lisata Therapeutics, Inc.¹

LSTA1 was designed to target tumor vasculature by its affinity for alpha-v integrins that are selectively expressed in tumors but not in healthy tissues.² Once the cyclic peptide binds to these integrins, it is cleaved by proteases that are expressed in the tumors. After it is cleaved to a CendR fragment, CendR binds to neuropilin-1; this results in the activation of a novel uptake pathway that permits drugs to effectively penetrate solid tumors.

Preclinical data have demonstrated the ability of the investigative agent to modify the tumor microenvironment to strengthen the delivery and efficacy of co-administered drugs in models of solid tumors. Moreover, in animal models of pancreatic cancer, the agent has also been shown to reduce immunosuppressive Tregs and to boost CD8-positive T cells in the tumor.

Lisata Therapeutics, Inc. shared plans to collaborate with investigators from the University of Tartu initiate a double-blind, placebo-controlled, proof-of-concept phase 2a clinical trial, which will evaluate the safety and efficacy of LSTA1 plus standard of care (SOC) in patients with newly diagnosed glioblastoma multiforme, in the coming months.¹

The trial will be conducted at sites throughout Estonia and Latvia, and the targeted enrollment is 30 patients. Specifically, study participants will be randomly assigned 2:1 to receive LSTA1 plus SOC temozolomide vs placebo plus temozolomide. The first patient is expected to receive study treatment in Q4 2023.¹

“Malignant glioma is one of the most aggressive and deadly malignancies,” Kristen K. Buck, MD, executive vice president of R&D and chief medical officer of Lisata Therapeutics, Inc., stated in a press release.¹ “This orphan drug designation acknowledges the high unmet medical need of this patient population as well as the potential of LSTA1 to benefit patients in this setting.”

LSTA1 is also under exploration in other clinical trials.² In the phase 2b ASCEND trial that is being co-funded by Lisata and the Australasian Gastro-Intestinal Trials Group in collaboration with University of Sydney’s NHMRC Clinical Trial Centre, LSTA1 plus gemcitabine and nab-paclitaxel (Abraxane) is being compared with placebo plus gemcitabine/nab-paclitaxel in patients with previously untreated metastatic pancreatic ductal adenocarcinoma. The target enrollment completion for this trial is late in Q2 of 2024, with earliest possible data released in 2024. A phase 1b/2a Chinese study, sponsored by QILU Pharmaceuticals, is also exploring the addition of the agent to the chemotherapy backbone in the same indication.

Additionally, the phase 1b/2 CENDIFOX trial that is being conducted in the United States is evaluating the addition of LSTA1 to neoadjuvant FOLFIRINOX (leucovorin, 5-fluorouracil, and irinotecan) with or without panitumumab (Vectibix) in patients with pancreatic, colon, and appendiceal cancers. This is an investigator-initiated effort that is being led by those at the University of Kansas Medical Center. The enrollment completion target for this trial is Q4 of 2023, with possible data readouts anticipated throughout 2023. Complete results from CENDIFOX are expected in 2024.¹