SOTIO Biotech has presented preclinical results of its BOXR T cell therapy platform and revealed it indicates a strong clinical path for its first transgene-expressing CAR-T cell as a potential treatment for solid tumors in adults with cancer.
The results were presented at the Society for Immunotherapy of Cancer’s (SITC) 37th annual meeting taking place in the U.S. Additional data was presented on the trial design of AURELIO-04, an ongoing phase 2 study evaluating the efficacy and safety of SOT101 in combination with pembrolizumab in patients with advanced solid tumors.
Radek Spisek, chief executive officer of SOTIO, said: “Preclinical results from the study of our BOXR T cell therapy platform indicate a strong clinical path for our first transgene-expressing CAR-T cell, BOXR1030, as a potential clinical treatment for the 90% of adult cancer patients with solid tumors.
SOTIO: strong clinical path
“The GOT2 infused CAR-T cell therapy improved metabolic fitness, increased cell survival and proliferative capacity of CAR-T cells when exposed to suppressive tumor microenvironments, indicating potentially improved access to solid tumors; a long-standing challenge for CAR-T and other cancer therapies to date. We look forward to initiating first-in-human safety studies of BOXR1030 in the coming months.”
Pratirodh Koirala, presenting author from SOTIO Biotech Inc. in the U.S. added: “CAR-T cell therapy has made significant strides in the treatment of hematological malignancies, yet solid tumors remain resistant to current CAR-T strategies due to suppression by the tumor microenvironment.
“The preclinical data presented at this year’s SITC annual meeting demonstrate a promising mechanism of action for SOTIO’s BOXR1030 and underscore the potential that GOT2-expressing CAR-T cells have for enhanced metabolic fitness or more durable early memory phenotypes – benefits which could improve clinical outcomes against solid tumors despite a suppressive tumor microenvironment.”
Improved metabolic fitness
The company said an analysis of the BOXR1030 T cell data show that the BOXR CAR-T cells co-expressing the metabolic gene GOT2 have a higher frequency of less differentiated stem cell memory T cell (TSCM) populations and more CD27+ cells in all memory T cell subsets, suggesting fewer terminally differentiated cells compared to control CAR-T cells lacking the GOT2 transgene.
SOTIO added that when BOXR1030 T cells were exposed to stressful conditions characteristic of difficult-to-penetrate tumor microenvironments such as low glucose and chronic stimulation, the cells exhibited improved metabolic fitness, increased cell survival and proliferative capacity, multiple characteristics of less differentiated or early memory T cell populations, and retention of effector functions relative to control CAR-T cells.
Spisek added: “Additionally, progressing our lead clinical asset, SOT101 into the Phase 2 AURELIO-04 study has been a significant clinical milestone for SOTIO. The trial size of 320 patients, all of whom are facing a variety of metastatic cancers that present high unmet needs, will enable us to significantly increase our data pool as SOT101 continues to advance through the clinic.”
Efficacy and safety
The design of the phase 2 AURELIO-04 study, launched by SOTIO in July of 2022, was presented by Aurélien Marabelle, immuno-oncologist from the drug development department at Gustave Roussy Cancer Center.
The AURELIO-04 study is a phase 2, open-label, single-arm, multicentered study of SOT101 in combination with pembrolizumab to evaluate the efficacy and safety in patients with multiple advanced solid tumor indications.
SOTIO: clinical trial collaboration
The solid tumor selection was based on previous pembrolizumab studies and/or data from other checkpoint inhibitors (CPI) and includes both CPI-relapsed and/or CPI-naïve tumors. The study will enroll up to a total of approximately 320 patients with a maximum of 50 to 57 per indication in Europe and the United States.
SOTIO entered into a clinical trial collaboration and supply agreement with MSD, a tradename of Merck & Co., Inc. USA. MSD supplies KEYTRUDA for the study. In a phase 1 study, SOT101 in combination with pembrolizumab has reported clinical benefit in 15 out of 19 patients with at least one post-baseline tumor assessment.