G1 Therapeutics, Inc. Initiates Phase 2 Trial to Support Antitumor Mechanism of Action of Trilaciclib in Tumor Microenvironment
December 01, 2021 at 07:00 am EST
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G1 Therapeutics, Inc. announced that the company has initiated a Phase 2, single arm, open-label study of trilaciclib in patients with early-stage triple negative breast cancer (TNBC) designed to further investigate the role of trilaciclib in modulating the anti-tumor immune response. Pathologic complete response endpoints are also being evaluated in this trial. Initial results of this study are expected in the second half of 2022. Patient recruitment in this trial is now underway. Approximately 30 patients will be enrolled in this Phase 2 multicenter, open-label, single-arm, neoadjuvant study. Up to three tumor tissue samples will be collected for assessment. Tumor tissue will be obtained at baseline prior to study drug administration. Patients will receive a single dose of monotherapy trilaciclib, followed by a tumor biopsy approximately one week later. Following the biopsy, patients will enter the treatment phase in which trilaciclib will be administered on Day 1 of each cycle of anthracycline/cyclophosphamide for four cycles followed by trilaciclib administered on Day 1 of each weekly cycle of taxane chemotherapy for 12 cycles. Immune checkpoint inhibitor and/or carboplatin may be added to therapy at the discretion of the investigator. Three to five weeks after the last dose of chemotherapy, patients will proceed to surgery at which time a third tumor tissue sample will be collected if the patient has residual disease. Study treatment will continue as per protocol to completion or early discontinuation of chemotherapy, until unacceptable toxicity, Investigator?s decision to withdraw the patient from study treatment, consent withdrawal, or the end of the study, whichever occurs first. The primary objective is to evaluate the immune-based mechanism of action of trilaciclib after a single-dose as measured by the change in the ratio of CD8+ tumor-infiltrating lymphocytes (TILs) to regulatory T cell (Tregs) in the tumor microenvironment. Key secondary and exploratory endpoints include: assessment of pathologic complete response (pCR) rate at the time of definitive surgery; evaluation of the safety and tolerability of trilaciclib in combination with standard neoadjuvant systemic therapies; tumor mRNA analyses and immunohistochemistry and peripheral blood immune profiling following trilaciclib; identification of molecular and cellular biomarkers in tumor or blood samples that may be indicative of clinical response/resistance, pharmacodynamic activity, and/or the mechanism of action of trilaciclib and other systemic treatments.
G1 Therapeutics, Inc. is a commercial-stage biopharmaceutical company. The Company is focused on the development and commercialization of small molecule therapeutics for the treatment of patients with cancer. The Company's lead commercial product, COSELA (trilaciclib), is a therapy indicated to proactively help protect bone marrow (myeloprotection) from the damage of chemotherapy. Its product portfolio consists of Trilaciclib and Lerociclib, both of which are CDK4/6 inhibitors, and a Cyclin-dependent kinase 2 (CDK2) inhibitor. Trilaciclib is a novel therapy designed to transiently arrest cells that are dependent on CDK4/6 for proliferation, including hematopoietic stem and progenitor cells (HSPCs), in the G1 phase. Lerociclib is a differentiated clinical-stage oral CDK4/6 inhibitor being developed for use in combination with other targeted therapies in multiple oncology indications. COSELA is a short-acting intravenous CDK4/6 inhibitor. Its CDK2 is an internally discovered inhibitor.