A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer

NCT ID: NCT04505826

Last Updated: 2025-08-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-13

Study Completion Date

2024-07-30

Brief Summary

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This clinical trial is a Phase I dose escalation and dose expansion and Phase II monotherapy open-label, first-in-human, multicenter study of OP-1250 in adult subjects with advanced and/or metastatic hormone receptor (HR)-positive, her2-negative breast cancer.

Detailed Description

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This is a Phase I dose escalation and dose expansion and Phase II monotherapy open--label, first--in--human study to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D), to characterize the safety and pharmacokinetic (PK) profile, and to estimate the preliminary anti-tumor activity of OP-1250 as a single agent in adult subjects with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic or locally advanced breast cancer. This study comprises 2 Phases: Phase I (Part A \[Dose Escalation\] and Part B \[Dose Expansion\]) and Phase II. Additionally, all subjects (Phase I and Phase II) will be eligible to participate in 1 of 2 sub-studies. Patients must have received at least 1 prior hormonal regimen and at least 6 months of a prior continuous endocrine therapy for locally advanced or metastatic disease. Patients will be evaluated for treatment emergent adverse events (AEs) during study participation, and toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0.

Conditions

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Hormone Receptor Positive Breast Carcinoma HER2-negative Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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OP-1250 Phase I Part A (Dose Escalation) and Part B (Dose Expansion)

Phase I Part A will evaluate the safety and pharmacokinetics (PK)of a range of OP-1250 doses to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Phase I Part B will evaluate the safety and PK of OP-1250 to confirm the RP2D dose.

Group Type EXPERIMENTAL

OP-1250

Intervention Type DRUG

Complete Estrogen Receptor ANtagonist (CERAN)

OP-1250 Phase II

This portion of the study further explores the clinical activity, safety, and PK of OP-1250 monotherapy at the RP2D and will estimate preliminary anti-tumor efficacy in 3 cohorts.

Cohort A will enroll subjects with measurable disease without evidence of CNS metastases; Cohort B will enroll subjects with non-measurable (evaluable) disease without evidence of CNS metastases; and Cohort C will enroll subjects with evaluable disease (measurable and non-measurable) with CNS metastases.

Group Type EXPERIMENTAL

OP-1250

Intervention Type DRUG

Complete Estrogen Receptor ANtagonist (CERAN)

Interventions

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OP-1250

Complete Estrogen Receptor ANtagonist (CERAN)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Must have received at least 1 prior hormonal regimen and at least 6 months of a prior continuous endocrine therapy for locally advanced or metastatic disease
* Must not have received prior oral endocrine therapy \< 2 weeks prior to first dose
* Must not have received prior, chemotherapy in 2 weeks or within 5 half-lives whichever is earlier, antibody therapy within 4 weeks or investigational therapy within 4 weeks or 5 half-lives whichever is earlier, prior to the first dose
* Adequate hepatic function
* Adequate renal function
* Normal coagulation panel
* Willingness to use effective contraception

Exclusion Criteria

* Gastrointestinal disease
* Significant renal disease
* Significant cardiovascular disease
* Significant ECG abnormalities
* Ongoing systemic bacterial, fungal, or viral infection (requiring antimicrobial therapy)
* Pregnancy or breastfeeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Olema Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Shilkrut, MD

Role: STUDY_DIRECTOR

Olema Pharmaceuticals, Inc.

Locations

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UCLA Hematology/Oncology

Los Angeles, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

University of Miami, Sylvester Comprehensive Cancer Center

Deerfield Beach, Florida, United States

Site Status

Advent Health

Orlando, Florida, United States

Site Status

Florida Cancer Center

Sarasota, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

OHSU Knight Cancer Institute

Portland, Oregon, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Macquarie University

Sydney, New South Wales, Australia

Site Status

Westmead

Westmead, New South Wales, Australia

Site Status

ICON Cancer Centre

Auchenflower, Queensland, Australia

Site Status

Cancer Research South Australia

Adelaide, South Australia, Australia

Site Status

Countries

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United States Australia

References

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Hamilton EP, Patel MR, Borges VF, Meisel JL, Okera M, Alemany CA, Pluard TJ, Wesolowski R, Sabanathan D, Miller KD, Conlin AK, McCarthy N, Shaw M, Tonda M, Shilkrut M, Lin NU. Palazestrant, a novel oral Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD), in patients with ER+/HER2- advanced or metastatic breast cancer: phase 1/2 study results. Breast Cancer Res. 2025 Jul 1;27(1):119. doi: 10.1186/s13058-025-02049-y.

Reference Type DERIVED
PMID: 40598566 (View on PubMed)

Other Identifiers

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OP-1250-001

Identifier Type: -

Identifier Source: org_study_id

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