A First-in-Human Phase 1 Study of a Novel Selective Androgen Receptor Modulator (SARM), RAD140, in ER+/HER2-...

Area of Science:

• Oncology
• Pharmacology
• Endocrinology

Background:

• Metastatic breast cancer (mBC) remains a significant health challenge.
• Selective androgen receptor modulators (SARMs) represent a novel therapeutic class.
• Androgen receptor (AR) signaling is implicated in certain breast cancer subtypes.

Purpose of the Study:

• To evaluate the safety, tolerability, and maximum tolerated dose (MTD) of RAD140.
• To characterize the pharmacokinetic (PK) profile of RAD140.
• To assess the preliminary antitumor activity and target engagement of RAD140 in patients with AR+/ER+/HER2- mBC.

Main Methods:

• A first-in-human, phase 1, dose-escalation study with a 3+3 design.
• Enrollment of postmenopausal women with heavily pretreated ER+/HER2- mBC.
• Use of serum sex hormone-binding globulin (SHBG) and prostate-specific antigen (PSA) as surrogate markers of AR engagement.

Main Results:

• RAD140 was administered at doses up to 150 mg daily, with an MTD of 100 mg/day.
• Most frequent treatment-emergent adverse events included elevated liver enzymes and gastrointestinal issues.
• Preliminary evidence of antitumor activity, including one partial response, and confirmed AR engagement via biomarker and biopsy data.

Conclusions:

• RAD140 is a novel oral AR-targeted agent for AR+/ER+/HER2- mBC.
• The agent demonstrated an acceptable safety profile in this initial study.
• Preliminary data suggest target engagement and antitumor activity warranting further investigation.