G1 Therapeutics presents first clinical data on Oral SERD G1T48
G1 Therapeutics announced preliminary results from a Phase 1/2a dose-escalation study of G1T48, an oral selective estrogen receptor degrader, in patients with estrogen receptor-positive, HER2-negative breast cancer. In the trial, G1T48 was well tolerated and demonstrated evidence of anti-tumor activity in heavily pre-treated patients. Safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of G1T48 were evaluated in an open-label, dose-escalation Phase 1 trial. The data reported are from 26 post-menopausal women with ER+, HER2- breast cancer who were eligible to receive up to three lines of prior chemotherapy in the metastatic setting and up to three endocrine therapies, including fulvestrant, aromatase inhibitors and tamoxifen, in the metastatic setting. This was a difficult to treat, heavily pre-treated population: 65% of patients had received greater than or equal to 3 lines of therapy, 85% of patients had prior treatment with fulvestrant and most had received one or more targeted therapies. Preliminary findings showed: G1T48 was well tolerated with no dose-limiting toxicities reported at any of the five dose levels studied; maximum tolerated dose was not reached. No patient experienced a serious adverse event related to G1T48. Seven patients remain on treatment. There was a dose-dependent increase in drug exposure; dosing with food reduced variability and increased exposure. Significant decreases in 18F-FES PET uptake during G1T48 treatment indicated target engagement for all doses tested. Of 19 patients with RECIST measurable tumors: The clinical benefit rate across all doses was 15.8%. Seven patients experienced stable disease across all doses. One patient experienced a confirmed partial response. Based on safety and tolerability findings in the Phase 1b portion of this trial, the company selected the 600 mg and 1,000 mg doses of G1T48 for evaluation in the ongoing Phase 2a portion and will use these data to select the dose for pivotal trials. The company plans to initiate a first-line Phase 3 trial of G1T48 in combination with an oral CDK4/6 inhibitor for the treatment of ER+, HER2- breast cancer in 2020.