On April 26, 2021 OBI Pharma, Inc., a Taiwan biopharma company (TPEx: 4174), reported that the U.S.-based SWOG Cancer Research Network has started patient enrollment for a Phase I/II study of OBI-3424, a first-in-class (small-molecule prodrug) DNA alkylating agent that targets cancers expressing the aldo-keto reductase 1C3 (AKR1C3) enzyme (Press release, OBI Pharma, APR 26, 2021, View Source [SID1234578513]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The study, S1905 (ClinicalTrials.gov Identifier: NCT04315324), is titled "A Phase 1/2 Study of AKR1C3-Activated Prodrug OBI-3424 in Patients with Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)/T-Cell Lymphoblastic Lymphoma (T-LBL)." SWOG is a member of the National Cancer Institute’s (NCI) National Clinical Trials Network (NCTN), America’s largest publicly funded cancer research network. In the NCTN, cancer trials are designed by some of the nation’s leading cancer experts, funded by tax dollars, and powered by patient volunteers.
OBI Pharma’s Chief Medical Officer, Tillman Pearce, M.D., noted, "This clinical trial intends to verify whether the potent efficacy that OBI-3424 demonstrated against T-ALL patient-derived xenografts in mice (Evans et al. Clin Ca Res 2019) can be observed in T-ALL and T-LBL patients. The initial xenograft experiments were conducted by the NCI Pediatric Preclinical Study Group, so it is very fitting that SWOG is the first to evaluate the concept in patients. This study in an unmet population of patients with T cell acute leukemias and lymphomas is complementary to OBI Pharma’s ongoing phase 1/2 study evaluating OBI-3424 in solid tumors (ClinicalTrials.gov Identifier: NCT03592264)."
Anjali S. Advani, MD, director of the Inpatient Leukemia Unit at Cleveland Clinic Taussig Cancer Institute and professor of medicine at Cleveland Clinic Lerner College of Medicine in Cleveland, OH is the lead investigator of the OBI-3424 T-ALL/T-LBL SWOG trial.
"Although the treatments in B-ALL have advanced significantly, we have lagged behind in T-ALL," said Dr. Advani. "We are hopeful that targeting AKR1C3 in T-ALL will represent a promising treatment strategy."
About OBI-3424
OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1C3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.
AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult-to-treat cancers including hepatocellular carcinomas (HCC), castrate-resistant prostate cancer (CRPC), and T-cell acute lymphoblastic leukemia (T-ALL). AKR1C3 is highly expressed in up to 15 solid and liquid tumors.
Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed based on tumor biopsies or circulating tumor cells to identify patients with other tumor types most likely to respond to treatment with OBI-3424, and thus offering the possibility for a streamlined clinical development strategy.