Benzinga | Aug 3, 2021 09:25AM EDT

Lixte Reports Its LB-100 Elicits Anti-Tumor Activity In Small Lung Cancer Models

Lixte Biotechnology Holdings, Inc. (NASDAQ:LIXT) announced that its lead clinical compound, LB-100, a protein phosphatase 2A (PP2A) inhibitor, was reported to enhance the effectiveness of elements of standard therapy in models of small cell lung cancer (SCLC) (Mirzapoiazova el al., Molecular Cancer Therapeutics, online July 12, 2021).

Dr. Ravi Salgia, MD, PhD, Professor and Chair of the Department of Medical Oncology and Therapeutics Research and Arthur & Rosalie Kaplan Chair in Medical Oncology, City of Hope, is the corresponding author of the paper. He is also the principal investigator for a recently opened Phase 1b clinical trial (NCT04560972) for patients with previously untreated advanced small cell lung cancer, in which LB-100 is added to a standard regimen of carboplatin, etoposide, and atezolizumab.

The subject clinical trial is funded by Lixte Biotechnology. Lixte's CEO, John S. Kovach, MD, and an author on the preclinical study (which was not funded by Lixte), commented that "Dr. Salgia and his scientific collaborators have carried out extensive pre-clinical studies of abnormal molecular features of SCLC and the effects of LB-100 on components of a standard regimen for the treatment of this disease. They found multiple metabolic changes associated with cell death in these cancer cells when exposed to LB-100 alone and when combined with the drugs in this standard clinical regimen for this notoriously aggressive disease."

Kovach continued "LB-100 has been reported to increase the effectiveness of a number of anti-cancer drugs against several different types of human cancers without increasing toxicity in animal models. Of note in the current preclinical study of SCLC cells is 1) that LB-100 increases the amount of carboplatin that enters the tumor cells without increasing toxicity, and 2) that LB-100 potentiates the action of the immune-blocker, atezolizumab."

These observations are of great interest to Lixte because, taken together, they not only constitute a strong rationale for the recently opened clinical trial of LB-100 plus chemo-immunotherapy in SCLC but they complement earlier preclinical observations that LB-100 can 1) reverse resistance of cancer cells (ovarian) to cisplatin, another widely used chemotherapy drug (Chang et al., Molecular Cancer Therapeutics, Nov. 5, 2014) 2), increase the entry of another important anti-cancer agent, doxorubicin, into liver cancer cells associated with increased antitumor activity (Bai et al, Molecular Cancer Therapeutics, Aug. 14, 2014) , and 3) enhance the effectiveness of immune-blockers against several types of cancers (Ho et al. Nature Comm., May 29, 2018). These observations raise the possibility that the addition of LB-100 may be a general way to enhance standard therapies for cancers for which better treatments are urgently needed. The present trial in SCLC is an initial step in testing that hypothesis.