The FDA has granted an orphan drug designation to TST001, an anti-Claudin18/2 monoclonal antibody, for the treatment of gastric cancer or gastroesophageal junction.
The FDA has granted an orphan drug designation to TST001, an anti-Claudin18/2 monoclonal antibody, for the treatment of gastric cancer or gastroesophageal junction (GC/GEJ), according to a press release by Transcenta Holding Limited.
Transcenta’s Immune Tolerance Breaking Technology platform generated TST001, which can kill Claudin18.2-expressing tumor cells by the way of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Preclinical and clinical data have found that TST001 has potent anti-tumor activity.
"GC/GEJ is a serious, life-limiting orphan disease in the United States [US]. At present, the treatment of GC/GEJ represents an urgent unmet clinical need globally. This ODD by the US FDA for the treatment of GC/GEJ marks an important milestone in the global development of TST001," said Michael Shi, EVP, Head of Global R&D and CMO of Transcenta, in a press release. "We will expedite the development of TST001 for GC/GEJ either as single agent or combination therapy to benefit patients around the world."
TST001 is currently being evaluated in 2 phase 1 studies of advanced or metastatic solid tumors.
The first phase 1 study (NCT04396821), has an estimated enrollment of 114 participants and an estimated completion date of April 2023. The non-randomized, parallel assignment study has primary end points of safety as defined by frequency and severity of adverse events (AEs) and maximum tolerated dose. The secondary end points include area under plasma concentration time versus time curve, peak plasma concentration, time to maximum observed plasma concentration, immunogenicity, objective response rate (ORR), duration of response (DoR), clinical benefit rate, progression-free survival (PFS).
The study is split into 2 parts. In part A there are 2 arms. In arm 1, patients receive the agent every 2 weeks at a starting dose of 1 mg/kg. Five dose levels will be tested. In arm 2 of part A, patients will receive the agent every 3 weeks with a starting dose of 3 mg/kg. Four dose levels will be tested.
Part B of the study has 3 arms. In cohort 1 of part B, patients will receive the recommended every 2-week dose. In cohort 2, patients with Claudin18.2 expressing tumors will receive the recommended every 2-week dose. In cohort 3, patients with Claudin18.2 expressing tumors will receive the recommended every 3-week dose.
In order to participate, patients must be intolerant to standard therapies or have progressed after standard therapies, have an ECOG performance status of 0-1 in part A and 0-2 in part B, have a life expectancy of ≥3 months, have at least one measurable disease, and have adequate organ function. Patients with central nervous system metastases, major surgery within 8 weeks prior to the study, or severe cardiovascular disease are not eligible to participate.
The second phase 1 trial of the agent (NCT04495296) has an estimated enrollment of 210 patients with an estimated competition date of January 1, 2023. It is a single group assignment, open label study and has the primary end points of safety as characterized by the frequency and severity of AEs, maximum tolerated dose, recommended phase 2 dose, and the incidence and case number of dose-limiting toxicities.
The secondary end points include area under plasma concentration versus time curve, peak plasma concentration, time to maximum observed plasma concentration, terminal elimination half-life, immunogenicity, ORR, DoR, and PFS.
The study has a single arm. All patients will receive a TST001 Injection. Additionally, the study will have 2 parts: a dose-escalation stage and a dose-expansion stage.
In order to participate, patients must be between 18 and 75 years of age, have an unresectable or metastatic malignant local solid tumor, and ECOG score between 0-1, and an expected survival of ≥3 months. Patients who received radiotherapy within 4 weeks prior to the initial dosing, major surgery within 8 weeks prior to initial dosing, symptoms of brain or leptomeningeal metastases, or patients suffering from body cavity effusion are not eligible to patriate.