A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)

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Investigational drug late phase More information Active drug More information Low burden on patient More information

Trial Details

Sponsor: Olema Pharmaceuticals, Inc. (industry)

Phase: 3

Start date: Nov. 16, 2023

Planned enrollment: 510

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chevron Show for: Palazestrant (OP-1250)

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Trial ID: NCT06016738
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More trial details at ClinicalTrials.gov More info

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Goal: To compare the safety and efficacy of palazestrant (OP-1250) monotherapy with standard-of-care endocrine therapy in patients with ER+, HER2- advanced or metastatic breast cancer that has progressed following prior endocrine therapy and CDK4/6 inhibitor treatment.

Patients: Adult women and men with ER+, HER2- advanced or metastatic breast cancer whose disease is not amenable to curative therapy, has relapsed or progressed on 1 or 2 lines of standard endocrine therapy (including a CDK4/6 inhibitor), with good performance status and adequate organ function. Key exclusions include symptomatic visceral disease, prior chemotherapy in the advanced/metastatic setting, prior investigational ER-targeted therapy, and active brain or leptomeningeal metastases.

Design: This is an international, multicenter, randomized, open-label, active-controlled phase 3 study. About 510 participants are randomized to receive either palazestrant or standard-of-care endocrine therapy. The trial includes an initial dose-selection phase followed by the main efficacy phase.

Treatments: The investigational arm is palazestrant (OP-1250), an oral complete estrogen receptor antagonist (CERAN) and SERD that fully blocks estrogen receptor signaling and induces receptor degradation, including in cases with ESR1 mutations. In prior phase 2 studies, palazestrant showed a median progression-free survival of 4.6-7.2 months and clinical benefit rates between 40-59% depending on the subgroup, with a favorable safety profile. The control arm is standard-of-care endocrine therapy, consisting of either fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane).

Outcomes: Primary endpoints include progression-free survival (PFS) by BIRC and safety/tolerability measures (incidence of adverse events, dose reductions, and drug discontinuations) during the dose-selection phase. Secondary outcomes include overall survival (OS). Efficacy is assessed separately for participants with and without ESR1 mutations.

Burden on patient: The patient burden for this trial is expected to be low to moderate. Both palazestrant and standard therapies are oral or parenteral agents commonly used in this setting, and additional procedures beyond standard oncologic care (such as routine imaging, labs, and clinical assessments) are not detailed. No mention is made of mandated biopsies or intensive PK sampling. Travel requirements should be similar to routine clinical follow-up. Overall, the trial procedures align with current standards for metastatic breast cancer clinical trials.

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