G1T38, an oral CDK4/6 inhibitor, dosed continuously in combination with fulvestrant for HR+ breast cancer: Preliminary phase 1b results.

1061Background: CDK4/6 inhibition has demonstrated significant improvements in PFS when combined with fulvestrant (F) in patients with breast cancer (BC). G1T38 (38) is a potent, selective oral CDK4/6 inhibitor with best-in-class potential. Continuous daily dosing in preclinical models inhibits tumor growth and leads to a dose-dependent ANC decline and subsequent plateau. A completed Phase 1 trial supports this Phase 1b/2a trial (NCT02983071) in BC patients. Methods: Patients with metastatic or locally advanced HR+ HER2(-) BC who had progressed following endocrine therapy are eligible. Patients receive 38 QD or BID continuously with 500 mg F. Primary objectives are to evaluate DLTs, safety, and tolerability and to determine the RP2D and schedule of 38 administered with F. Results: To date, 24 patients (median age 55.5) have enrolled and received 38 doses ranging from 200-500 mg QD and 100-150 mg BID for up to 367 days. Dose escalation is ongoing. 38 is well tolerated: no 38-related SAEs have been reported...