Dr McArthur on Data Supporting the Ongoing Investigation of Palazestrant in ER+, HER2– Breast Cancer

“[Palazestrant generated] very encouraging response rates in this heavily pretreated population. The adverse effects that occurred were typically low grade.”

Heather McArthur, MD, MPH, FASCO, the clinical director of breast cancer and the Komen Distinguished Chair in Clinical Breast Cancer Research at the University of Texas Southwestern Medical Center, discussed data from a phase 1/2 study (NCT04505826) evaluating palazestrant (OP-1250) in patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer.

Findings from the phase 1/2 study revealed that patients who received palazestrant at 60 mg (n = 26) experienced an overall response rate (ORR) of 11.5% and a clinical benefit rate (CBR) of 19.2% (95% CI, 6.6%-39.4%). The CBR among patients with ESR1-mutated disease (n = 13) was 23.1% (95% CI, 5.0%-53.8%). Patients with measurable disease who received the 120-mg dose (n = 66) achieved an ORR of 7.6%. The CBR was 45.7% (95% CI, 33.7%-58.1%) among all patients (n = 70) and 58.6% (95% CI, 38.9%-76.5%) among patients with ESR1-mutated disease (n = 29).

McArthur noted that the population was heavily pretreated; despite this, the response rates observed with palazestrant were encouraging, she added. In terms of safety, adverse effects (AEs) were typically low grade, she noted. Less than 6% of patients in the safety population discontinued treatment due to AEs, she said. Grade 4 neutropenia occurred in approximately 7% of patients, but the agent was well tolerated overall, she said.

In light of these findings, investigators have initiated the phase 3 OPERA-01 trial (NCT06016738), which is comparing palazestrant monotherapy with standard-of-care endocrine therapy in patients with ER-positive, HER2-negative advanced or metastatic breast cancer. OPERA-01 is composed of 2 parts, McArthur stated. Multiple doses of palazestrant were evaluated in part 1; based on the outcomes in part 1, a dose was selected for further evaluation in the dose-expansion phase, McArthur explained. The study has been reopened and is recruiting patients, she added.

Palazestrant is also being examined in the frontline setting alongside the CDK4/6 inhibitor ribociclib (Kisqali) in the phase 3 OPERA-02 trial (NCT07085767), McArthur concluded.