Olema Oncology Reveals New Data on Palazestrant and Ribociclib at 2024 ESMO Breast Cancer Congress

Olema Pharmaceuticals, Inc., a biopharmaceutical company dedicated to developing targeted therapies for women's cancers, has announced interim results from its ongoing Phase 1b/2 clinical study. This study evaluates the efficacy and safety of palazestrant (OP-1250) in combination with the CDK4/6 inhibitor ribociclib for treating ER+/HER2- metastatic breast cancer.

The data, collected as of March 13, 2024, will be presented on May 16, 2024, at the ESMO Breast Cancer Annual Congress in Berlin. The study poster, titled “A Phase 1b/2 Study of Palazestrant (OP-1250) in Combination with Ribociclib in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Advanced and/or Metastatic Breast Cancer,” highlights several key findings.

Among the 50 treated patients, the combination of up to 120 mg of palazestrant with the approved dose of 600 mg of ribociclib daily was generally well-tolerated. There were no new safety signals or enhanced toxicity, and no significant impact on the drug exposure of either therapy was observed. Notably, the clinical benefit rate (CBR) was 85% across all eligible patients, indicating promising preliminary efficacy.

Specifically, the CBR was 83% in ESR1-mutant patients, 86% in ESR1-wild-type patients, and 83% in prior CDK4/6 inhibitor patients. Partial responses were observed in five patients, with two confirmed and three unconfirmed responses among the 23 patients evaluated for response. These findings support the continued clinical development of palazestrant combined with ribociclib for the first-line treatment of ER+/HER2- advanced or metastatic breast cancer.

“The data presented at the ESMO Breast Cancer Annual Congress bolster our belief that palazestrant has the potential to become a preferred endocrine therapy for ER+/HER2- breast cancer, either alone or in combination with other targeted therapies,” said Sean P. Bohen, M.D., Ph.D., President and CEO of Olema Oncology. He expressed gratitude to the approximately 300 women who participated in the clinical trials and is optimistic about the progress made towards transforming the endocrine therapy standard of care for breast cancer.

As of the data cut-off, 50 patients with recurrent, locally advanced, or metastatic ER+/HER2- breast cancer had been treated with palazestrant and ribociclib. The majority had previously received endocrine therapy and CDK4/6 inhibitors, with some also having undergone chemotherapy. The study is now fully enrolled with 60 patients.

In terms of pharmacokinetics, palazestrant exhibited high oral bioavailability and dose proportional exposure, with a half-life of eight days, allowing for consistent ER inhibition throughout the dosing interval. The combination treatment did not affect ribociclib drug exposure, and palazestrant showed no significant difference in steady-state trough levels when used alone or in combination.

Safety and tolerability were favorable, with no dose-limiting toxicities observed at the recommended Phase 2 dose of 120 mg. The majority of adverse events were Grade 1 or 2 in severity. Ten patients required dose reductions of ribociclib due to QTcF prolongation, neutropenia, or fatigue, but none discontinued palazestrant due to adverse events. Neutropenia was reversible and consistent with known ribociclib-related effects.

In terms of efficacy, palazestrant demonstrated anti-tumor activity and prolonged disease stabilization in both ESR1 wild-type and mutant patients. Partial responses were noted in five patients, contributing to an overall CBR of 85% among all eligible patients. As of the data cut-off, 66% of the 50 patients remained on treatment, with the longest duration being 44 weeks.

These interim results suggest that the palazestrant-ribociclib combination holds potential as a first-line treatment for ER+/HER2- advanced or metastatic breast cancer, paving the way for further clinical development.