Olema Oncology, a clinical-stage biopharmaceutical company, has recently announced promising interim results from a phase 1b/2 clinical study of palazestrant (OP-1250) in combination with the CDK4/6 inhibitor ribociclib for the treatment of ER+/HER2* metastatic breast cancer.
The combination of up to 120 mg of palazestrant with the full and approved dose of 600 mg of ribociclib daily was well tolerated across 50 treated patients, with no new safety signals or enhancement of toxicity. Palazestrant did not affect ribociclib drug exposure, and ribociclib had no clinically meaningful effect on palazestrant drug exposure.
Key preliminary efficacy findings include an 85% clinical benefit rate (CBR) observed across all CBR-eligible patients, with partial responses observed in five patients through the data cut-off. Additionally, the data showed promising preliminary efficacy with an 85% CBR across all CBR-eligible patients, 83% in ESR1-mutant patients, 86% in ESR1-wild-type patients, and 83% in prior CDK4/6 inhibitor patients.
The study also demonstrated favorable pharmacokinetics, with palazestrant showing high oral bioavailability, dose-proportional exposure, and a half-life of eight days as a single agent. The treatment with palazestrant up to the recommended phase 2 dose of 120 mg was well tolerated, with no dose-limiting toxicities, and the maximum tolerated dose was not reached.
In terms of efficacy, palazestrant showed anti-tumor activity and prolonged disease stabilization in patients with ESR1 wild-type and ESR1 activating mutations at baseline, as well as in those previously treated with one or two lines of CDK4/6 inhibitors. The longest duration on treatment is 44 weeks through the data cut-off, and 66% of patients in this data set remain on treatment as of the data cut-off date.
Palazestrant, a novel, orally-available small molecule with dual activity as both a complete estrogen receptor antagonist (CERAN) and selective ER degrader (SERD), has demonstrated anti-tumor efficacy along with favorable tolerability, CNS penetration, and combinability with CDK4/6 inhibitors. It has been granted U.S. Food and Drug Administration (FDA) fast track designation for the treatment of ER+/HER2* metastatic breast cancer.
These results support the continued clinical development of palazestrant in combination with ribociclib for the first-line treatment of ER+/HER2* advanced or metastatic breast cancer. Olema Oncology is focused on transforming the endocrine therapy standard of care for breast cancer and is encouraged by the progress made in this study. Today the company's shares have moved 0.9% to a price of $10.26. If you want to know more, read the company's complete 8-K report here.
