FDA Grants ODD to LSTA1 for Advanced Solid Tumor Treatment


Early clinical trial in gastrointestinal and brain cancers aim to better understand the safety and efficacy of CEND-1-targeted therapy and develop a novel CEND-1 agent.

  • LSTA1 has potential to fill an unmet need for novel treatments to address advanced solid tumors.

  • Multiple studies are examining the investigational drug in patients with advanced pancreatic ductal adenocarcinoma (PDAC).

  • A new designation awarded by the FDA could give LSTA1 7 years of market exclusivity, if later granted an FDA approval.

The FDA has granted orphan drug designation to LSTA1 for the treatment of patients with advanced solid tumors.1

LSTA1 is a an investigational CEND-1 targeting agent that is designed to be combined with anti-cancer drugs to better invade solid tumors. The agent has demonstrated ability to alter the tumor microenvironment to make immunotherapies more effective in these tumors. In clinical trials of patients with pancreatic cancer, LSTA1 showed activity along with agreeable safety and tolerability.

In a phase 1 study (NCT03517176) that assessed the use of CEND-1 targeted therapy in combination with nab-paclitaxel and gemcitabine in patient with PDAC, promising activity was shown along with an acceptable safety profile. The study included 31 patients, 8 of whom were treated in the dose-escalation cohort and 23 of whom were treated with the combination in the dose-expansion cohort.2

The efficacy results were exclusive of data from 2 patients, leaving 29 patients evaluable for efficacy. The objective response rate observed was 59%, which included 1 complete response and 16 partial responses. Median follow-up for survival was 26 months (interquartile range, 24-30 months), and the median overall survival was 13.2 months (95% CI, 9.7-22.5 months).

All 31 patients were evaluable for safety. Overall, there were no CEND-1 dose-limiting toxicities observed during the dose-escalation phase of the study. The most common grade 3 or 4 adverse (AEs) events observed included neutropenia (55%), anemia (62%), leukopenia (16%), and pulmonary embolism (13%). These AEs were consistent with nab-paclitaxel and gemcitabine. There were serious AEs observed 71% of patients, and most cases resulted from disease progression.

Overall, 10 patients in the study died. Death was due to disease progression for 9 patients, and the 10th patient had left middle artery stroke.

Illustration of cells in blue | Image Credit: © Jezper - www.stock.adobe.com

Blue cancer cell | Image Credit: © Jezper - www.stock.adobe.com

Other studies of LSTA1 in PDAC are ongoing, including the phase 1/2 study of LSTA1 for injection in patients with advanced/metastatic PDAC (NCT05052567)3, and the phase 2 ASCEND study (NCT05042128) of LSTA1 plus gemcitabine and nab-paclitaxel or placebo for the treatment of untreated metastatic PDAC.4 LSTA1 is also being investigated in the phase 1/2 CENDIFOX study (NCT05121038).5 CENDIFOX is evaluating with or without panitumumab (Vecitibix) in patients with either pancreatic cancer, colon cancer, or appendiceal cancers.5 The developer of LSTA1, Lisata Therapeutics, is also planning to explore its use on patients with glioblastoma multiforme. A new trial for this patient population is expected to launch in the fourth quarter of 2023.1

With an orphan drug designation, there will be financial incentives to help with the clinical development of LSTA1. The agent will also have a 7-year term of market exclusivity, if later granted FDA approval.

“Malignant glioma is one of the most aggressive and deadly malignancies,” stated Kristen K. Buck, MD, executive vice president of research and development and chief medical officer of Lisata, in a press release. “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.”


1. 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 August 9, 2023. https://tinyurl.com/2pvvuaja

2. Dean A, Gill S, Mcgregor M, Broadbridge V, Järveläinen HA, and Price T. Dual αV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic pancreatic ductal adenocarcinoma: a first-in-human, open-label, multicentre, phase 1 study. Lancet Gastroenterol Hepatol. 2022 Oct;7(10):943-951. doi:10.1016/S2468-1253(22)00167-4.

3. CEND-1 injection (QLC12102) in patients with advanced metastatic pancreatic ductal adenocarcinoma. ClincialTrials.gov. Updated January 13, 2023. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05052567?term=NCT05052567&draw=2&rank=1

4. The ASCEND Study: Gemcitabine and nab-paclitaxel with CEND-1 or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma (ASCEND). Updated January 26, 2023. Accessed august 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05042128?term=NCT05042128&draw=2&rank=1

5. CEND-1 in combination with neoadjuvant folfirinox with or without panitumumab (CENDIFOX). ClinicalTrials.gov. Updated November 24, 2021. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05121038?term=NCT05121038&draw=2&rank=1

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