1069 Background: Androgen receptor (AR) targeting therapy has shown single agent activity in triple negative breast cancer (TNBC). GTx-024, a nonsteroidal selective androgen receptor modulator (SARM), demonstrated preclinical and clinical activity in AR+ breast cancer. The current study is designed to test the safety and efficacy of GTx-024 and pembrolizumab in patients with AR+ metastatic TNBC (mTNBC). Methods: This is an open-label phase 2 study for AR+ mTNBC. Eligible participants receive pembrolizumab 200mg IV every 3 weeks in combination with GTx-024 18mg po daily. Key eligibility criteria include patients with AR+ ( > 10%, 1+ by IHC); mTNBC; ECOG 0-1; measurable disease per RECIST 1.1. Patients are excluded if they had prior checkpoint inhibitors or AR targeted agents. The primary objective is to evaluate the tolerability of GTx-024 and pembrolizumab, and determine the response rate. Results: Seventeen patients were enrolled in the study. One patient was ineligible due to previously undiagnosed brain metastases. Ten of 16 patients had visceral metastasis (lung or liver), and 15% of patients had received ≥ 3 previous lines of therapy for mTNBC. Among 16 patients evaluable for response, 2 patients achieved a best response of partial response (PR), 2 patient had stable disease (SD, 18 and 19 weeks ), 11 patients had progressive disease (PD), and 1 patient is too early for restaging imaging. Durable response was found in 1 patient. Grade 3 toxicities include 1 diarrhea and 1 dry skin. Grade 2 adverse events include 3 elevated liver function, 1 adrenal insufficiency, 1 hyperthyroidism, 1 palpitation, 1 diarrhea, 1 hyperhydrosis, 1 hot flashes and 1 headache. Three patients had dose delay and two patients had dose reduction. Conclusions: AR targeted therapy GTx-024 combined with pembrolizumab is well tolerated with clinical activity. Clinical trial information: NCT02971761.
Phase I dose escalation study of a selective androgen receptor modulator RAD140 in estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer (BC)
