palazestrant + ribociclib

The combination of palazestrant (OP-1250) and ribociclib (Kisqali) is being investigated for the treatment of estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer. This combination has shown promising preliminary efficacy and a favorable safety profile in clinical trials. Palazestrant is a novel, orally available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It works by completely blocking ER-driven transcriptional activity in both wild-type and mutant forms of breast cancer cells. Ribociclib is an approved CDK4/6 inhibitor marketed under the brand name Kisqali. In clinical trials, the combination has demonstrated promising efficacy with a favorable safety profile. As of March 2024, in a Phase 1b/2 trial, the combination led to a clinical benefit rate of 85% across all eligible patients, 83% in patients with ESR1-mutated disease, 86% in patients with ESR1-wild-type disease, and 83% in patients previously treated with a CDK4/6 inhibitor. The 6-month progression-free survival rate was 73% in all patients, 81% in patients with ESR1 mutations, 70% in ESR1 wild-type patients, and 68% in patients with prior CDK4/6 inhibitor treatment. The combination is being evaluated at a dose of 120 mg of palazestrant with the approved dose of 600 mg of ribociclib daily. The treatment has been well-tolerated with no dose-limiting toxicities, and the majority of treatment-emergent adverse events were Grade 1 or 2. The combination shows particular promise in addressing ESR1 mutations, which are one of the most common resistance mechanisms arising during current front-line standard of care treatment. The data suggest that palazestrant combined with ribociclib may be effective regardless of ESR1 status, potentially offering a new treatment option for patients who have progressed on current standard therapies.

Other names

Palazestrant + Kisqali