FDA Fast Tracks OP-1250 for HR+, HER2- Metastatic Breast Cancer Treatment


The developer of OP-1250 anticipates working closely with the FDA to expedite the development of the drug for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer.

The FDA has granted fast track designation to OP-1250 for the treatment of patients with HER2-negative metastatic breast cancer (mBC) that has progressed following 1 or more lines of endocrine therapy with at least 1 line given in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor.1

OP-1250 is a novel, oral complete estrogen receptor (ER) antagonist and selective ER degrader (SERD). In a preclinical study, it was shown that OP-1250 antagonizes both AF1 and AF2 of the ER and degrades the receptor, which cause the tumor to shrink. The preclinical efficacy of OP-1250 included mBC xenograft models that expressed wild type and mutant receptors.2

“Receiving fast track designation from the FDA for OP-1250 is an important milestone for the development program and underscores OP-1250’s potential clinical utility to address a significant unmet medical need in women living with advanced ER-positive/HER2-negative breast cancer,” said Sean P. Bohen, MD, PhD, president, and chief executive officer of Olema Oncology, in a press release.1

To continue to evaluate the potential of OP-1250 in hormone receptor (HR)-positive, HER2-negative mBC, 2 clinical trials of the agent are ongoing.

A phase 1/2 dose-escalation and dose-expansion study (NCT04505826) has a target enrollment of 94 patients. The study aims to determine the maximum-tolerated dose of OP-1250.1,3

Eligible patients for the phase 1/2 study are those with an ECOG performance status of 0 or 1, who received prior oral endocrine therapy > 2 weeks prior to first dose and prior fulvestrant, chemotherapy, antibody therapy, or investigational therapy ≤ 4 weeks prior to the first dose. All patients are required to adequate hepatic and renal function, normal coagulation panel, and be willing to use contraception during the study.3

The study will exclude patients with gastrointestinal disease, significant renal disease, cardiovascular disease, electrocardiogram abnormalities, persistent systemic bacterial, fungal, or viral infection that requires antimicrobial treatment, and those who are pregnant or breast feeding.

In a phase 1b dose-escalation and dose-expansion study, OP-1250 is also being studied in combination with the CDK 4/6 inhibitor palbociclib (Ibrance) in patients with HR-positive, HER2-negative mBC (NCT05266105). The study aims to include 30 patients to determine the incidence of dose-limiting toxicities, characterization and incidence in adverse events and serious adverse events, and the plasma levels of OP-1250 and palbociclib.4

The study is actively recruiting patients who have confirmed and evaluable mBC, an ECOG performance score of 0 or 1, and adequate safety laboratory tests. Patients are required to have been previously treated with oral endocrine or targeted therapy ≤ 2 weeks prior to first dose, chemotherapy, antibody therapy, or investigational therapy ≤ 4 weeks prior to the first dose, and radiotherapy must have been completed 2 weeks prior to first dose. Patients also must be willing to use effective contraception during the study.

Individuals with gastrointestinal disease, and significant hepatic disease, cardiovascular disease, ECG abnormalities are ineligible to enroll. The study also excludes patients who have a history of pulmonary embolism or high-risk of thrombosis, known HIV infection, active infection, or who are pregnant.

“We look forward to working closely with the FDA to optimize and expedite the development program, with the goal of making OP-1250 available to patients sooner,” said Bohen, in the press release.


1. Olema Oncology receives FDA fast track designation for OP-1250 for the treatment of ER+ / HER2- metastatic breast cancer. News release. Olema Pharmaceuticals, Inc. July 21, 2022. Accessed July 21, 2022.

2. Hodges-Gallagher L, Sun R, Myles D, et al. OP-1250: A potent orally available complete antagonist of estrogen receptor-mediated signaling that shrinks wild type and mutant breast tumors. Eur J Cancer. 2020: 138(2):S55. soi: 10.1016/S0959-8049(20)31223-5

3. A dose escalation/expansion study of Oral OP-1250 in subjects with advanced and/or metastatic HR+, HER2- breast cancer. Clinicaltrials.gov. Updated October 25, 2021. Accessed July 21, 2022.

4. A phase 1 study of oral OP-1250 in combination with palbociclib in HR+/HER2- breast cancer patients. Clinicaltrials.gov. Updated March 4, 2022. Accessed July 21, 2022.

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