Abstract OT2-01-10: A phase 1 study of RAD1901, a novel, orally available, selective estrogen receptor degrader, for the treatment of ER positive advanced breast cancer

The current NCCN treatment guidelines for ER+ breast cancer involves the use of approved agents such as fulvestrant, tamoxifen and aromatase inhibitors that either inhibit estrogen production or block estrogen receptor binding. While the initial treatment regimens with these selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) is often successful, many women eventually relapse with more aggressive forms of endocrine-resistant disease. To begin to overcome some of the challenges associated with current therapies including exposure limitations and intramuscular administration, we have developed RAD1901, a novel, non-steroidal, orally available SERD. Preclinical studies with RAD1901 have demonstrated potent dose dependent ER degradation consistent with a SERD mechanism of action, as well as potent inhibition of proliferation in vitro in breast cancer cell lines. RAD1901 also demonstrated significant anti-tumor efficacy in vivo, and notably single agent regressions in both MCF7 and a primary patient derived xenograft models harboring an ESR1 mutations.A phase 1 monotherapy study conducted in healthy postmenopausal female volunteers evaluated forty four subjects treated once daily with RAD1901 with doses ranging from 200 mg/day up to 1000 mg/day for 7 days. All dose levels were generally well tolerated and pharmacokinetic analysis demonstrated plasma exposures consistent with preclinical efficacy in ER+ breast cancer models. Furthermore,...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Ongoing Clinical Trials Source Type: research