Olema Oncology presented updated clinical results from its Phase 1b/2 study of palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS 2024), showcasing promising activity and tolerability in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer.
The data, with a cutoff date of November 11, 2024, highlight the potential of this combination therapy, particularly in patients with ESR1 mutations, a common resistance mechanism to standard endocrine therapies. The study enrolled 62 patients, with the majority having received prior endocrine therapy and CDK4/6 inhibitors. Palazestrant was administered at a dose of 120 mg once daily, combined with ribociclib at 600 mg once daily (three weeks on, one week off).
Efficacy and Survival
The combination of palazestrant and ribociclib demonstrated encouraging clinical activity, including tumor responses and prolonged disease stabilization. With a median follow-up of 12 months, the median progression-free survival (PFS) had not been reached. The 6-month PFS rate across all patients was 73%. Notably, the 6-month PFS rate was 81% in patients with ESR1 mutations and 70% in ESR1 wild-type patients. In patients who had previously received a CDK4/6 inhibitor plus endocrine therapy, the 6-month PFS rate was 68%.
The clinical benefit rate (CBR) in CBR-eligible patients was 76% overall, 81% in those with ESR1 mutations, and 74% in ESR1 wild-type patients. Among response-evaluable patients with measurable disease, the objective response rate (ORR) was 27% (10/37), with 60% of these patients experiencing a reduction in target lesion size.
Safety and Tolerability
The combination of palazestrant and ribociclib was well-tolerated, with no new safety signals or increased toxicity observed. The safety profile was consistent with that of ribociclib 600 mg plus endocrine therapy. Most treatment-emergent adverse events (TEAEs) were Grade 1 or 2, and their severity and incidence aligned with the expected safety profile of ribociclib plus endocrine therapy. Pharmacokinetic data indicated that palazestrant did not affect ribociclib drug exposure.
Implications and Future Directions
Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology, stated, "These data provide the foundation to initiate OPERA-02, our planned pivotal Phase 3 trial of palazestrant in combination with ribociclib in front-line metastatic breast cancer next year." Virginia Borges, M.D., Professor at the University of Colorado, added, "The findings presented at SABCS show that the combination of palazestrant and ribociclib is well-tolerated with meaningful preliminary efficacy that I believe has the potential to outperform the current standard of care and change how metastatic breast cancer is treated."
These findings support the further clinical development of palazestrant in combination with ribociclib as a potential first-line treatment for ER+/HER2- advanced or metastatic breast cancer. Olema Oncology plans to present mature data from this combination in 2025 and continue the development of palazestrant to improve outcomes for breast cancer patients.
