Abstract
Abstract only e16527 Background: GT0918 is a new chemical entity of AR blocker. A phase I dose escalation study was planned for 6 dose cohorts in pts with mCRPC who have progressed on SoC and experimental therapies. No DLT or major toxicity was found in planned doses, therefore a cohort of 600 mg daily was added in December 2018. Methods: Patients (pts) with histologically confirmed mCRPC who progressed on enzalutamide +/- abiraterone and docetaxel were eligible. GT0918 was administered once daily orally for 28 consecutive days for DLT assessment. Pts could continue on GT0918 until they experienced intolerable toxicity, disease progression or withdrew consent. All pts consented for exploratory biomarker studies of CTC and cf-DNA/RNA. Results: 40 pts were treated with GT0918 in 7 cohorts. Pts had metastatic disease to bone only (44%), and lymph node +/-visceral +/- bone (56%), who progressed on multiple lines of therapies including but not limited to abiraterone, enzalutamide, docetaxel, cabazitaxel. GT0918 related adverse events (AEs) were grade 1 or 2 as per CTCAE v4.03. including fatigue, anemia, nausea, loss of appetite, hot flushing, depression, etc. The most common TEAE is fatigue and all pts at 500 mg dose reported having fatigue and one pt required dose reduction. Toxicity at the 600mg is still being analyzed but at least 2 pts had tremor. Treatment duration showed more pts in the treatment of 400 mg and 500 mg with SD in this heavily pretreated group (see Table). Exploratory biomarkers of CTCs also suggested higher dose of GT0918 resulted in better clinical outcomes. Conclusions: GT0918 administrated orally once daily was well tolerated. Better clinical outcomes were shown in dose cohorts of 400 mg and 500 mg without major toxicities. Thus these 2 doses were selected for dose expansion. Table. Clinical outcomes of GT0918 in heavily pretreated mCRPC pts Clinical trial information: NCT02826772. [Table: see text]