Palazestrant With Ribociclib Shows Promising Early Results in ER+/HER2- mBC


Findings from a phase 1b/2 study support the continued development of palazestrant plus ribociclib for patients with estrogen receptor-positive/HER2-negative metastatic breast cancer.

Breast Cancer - Female Anatomy - pain concept: © -

Breast Cancer - Female Anatomy - pain concept: © -

Treatment with palazestrant (OP-1250) given in combination with ribociclib (Kisqali), a CDK4/6 inhibitor, showed promising preliminary efficacy in patients with estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer, according to interim results from an ongoing phase 1b/2 trial (NCT05508906) presented in a poster session at the 2024 European Society for Medical Oncology Breast Cancer Annual Congress in Berlin, Germany (ESMO Breast).1

As of the data cutoff date of March 13, 2024, 50 patients were given the combination, which consisted of treated 120 mg of palazestrant with the full and approved dose of 600 mg of ribociclib daily. The combination led to a clinical benefit rate (CBR) of 85% across all patients who were eligible (11/13), 83% in patients with ESR1-mutated disease (5/6), 86% in patients with ESR1-wild-type disease (6/7), and 83% in patients treated with a prior CDK4/6 (10/12).

For safety, the combination was well-tolerated, and there were no new safety signals observed. Additionally, the overall safety profile of ribociclib was consistent with what has previously been observed with the agent when given with an endocrine therapy.

“The data we are presenting at the ESMO Breast Cancer Annual Congress in Berlin add further support to our thesis that palazestrant possesses key characteristics that make it a potential backbone endocrine therapy of preference for ER+/HER2[-negative] breast cancer, both as a monotherapy and in combination with other targeted agents,” said Sean P. Bohen, MD, PhD, president and chief executive officer of Olema Oncology, in a press release.

Fifty patients with recurrent, locally advanced or metastatic ER-positive/HER2-negative breast cancer with at least 4 weeks of follow-up, received palazestrant, including 3 patients each who were treated with the agent at 30 mg once daily and 60 mg once daily and 44 patients who were given the recommended phase 2 dose of palazestrant at 120 mg once daily. This was given in addition to ribociclib 600 mg once daily, which was given 3 weeks on followed by 1 week off treatment.

A total of 74% (n = 34) received prior endocrine therapy, and 70% (n = 35) received prior CDK4/6 inhibitors, including 11 who received 2 prior lines of CDK4/6 inhibitors and 9 who received chemotherapy. Forty-eight patients had circulating tumor DNA assessed as of the data cutoff. Of these patients, 27% had activating mutations in ESR1 at baseline.

Additional findings showed that 5 of the 23 response-evaluable patients had a partial response through the data cutoff, 2 of which were confirmed and 3 which were unconfirmed. Palazestrant also demonstrated antitumor activity and prolonged disease stabilization in a maturing dataset of patients with ESR1 wild-type and ESR1-activating mutations at baseline. This was also true for patients who had received 1 or 2 prior lines of CDK4/6 inhibitors.

Moreover, the longest duration of treatment is 44 weeks through the data cutoff, and 30 of the 50 patients included in this data set (66%) are continuing to receive treatment as of the data cutoff date.

These results support further development of this combination of palazestrant with ribociclib for the first-line treatment of patients with ER-positive/HER2-negative advanced or metastatic breast cancer.

“We are grateful to the approximately 300 women to date that have participated across our clinical trials. We are excited with the progress we are making, and we look forward to advancing toward our goal of transforming the endocrine therapy standard of care for breast cancer,” added Bohen, in the press release.

About Palazestrant

Palazestrant is a novel, orally available small molecule that has dual activity as a complete ER antagonist (CERAN) and selective ER degrader. The agent is currently undergoing investigation in trials for the treatment of recurrent, locally advanced or metastatic ER-positive/HER2-negative breast cancer.

Palazestrant was previously given a fast track designation from the FDA for ER-positive/HER2-negative metastatic breast cancer that has progressed following 1 or more lines of endocrine therapy with at least 1 line given with a CDK4/6 inhibitor.

As a single agent, palazestrant is being evaluated in the ongoing, phase 3 OPERA-01 trial (NCT06016738). Phase 1/2 combination studies are also evaluating palazestrant when given with CDK4/6 inhibitors like palbociclib (Ibrance); ribociclib; alpelisib (Vijoice), which is a PI3Ka inhibitor; and the mTOR inhibitor everolimus.

  1. Olema Oncology announces promising new data for palazestrant in combination with ribociclib presented at the 2024 ESMO breast cancer congress. News release. Olema Pharmaceuticals, Inc. May 15, 2024. Accessed May 16, 2024.
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