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

NCT04505826 | Completed Phase 1 FDA Drug

• 1 other identifier: OP-1250-001
• Study Type: interventional
• Target: 153
• Locations: 2 countries
• Sites: 19

Brief Summary

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.

Conditions

Hormone Receptor Positive Breast Carcinoma; HER2-negative Breast Cancer

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicities (DLT)

  To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of OP-1250, the incidence of DLTs will be assessed.

  The first 28 days of treatment

• Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250

  Characterize the incidence, nature and severity of TEAEs and SAEs of OP-1250 according to NCI-CTCAE version 5.0

  Up to 42 days after end of treatment

• Pharmacokinetics of OP-1250

  Plasma concentrations of OP-1250 will be assessed at predefined intervals

  Every 28 days

• Anti-tumor activity of OP-1250

  Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines

  Every 8 weeks

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: OP-1250

OP-1250 Phase II

EXPERIMENTAL

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.

Drug: OP-1250

Interventions

OP-1250 DRUG

Complete Estrogen Receptor ANtagonist (CERAN)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Olema Pharmaceuticals, Inc.: lead

Study Sites (19)

UCLA Hematology/Oncology

Los Angeles, California, 90404, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Deerfield Beach, Florida, 33442, United States

Location

Advent Health

Orlando, Florida, 32804, United States

Location

Florida Cancer Center

Sarasota, Florida, 34232, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Macquarie University

Sydney, New South Wales, 2109, Australia

Location

Westmead

Westmead, New South Wales, 2145, Australia

Location

ICON Cancer Centre

Auchenflower, Queensland, 4066, Australia

Location

Cancer Research South Australia

Adelaide, South Australia, 5000, Australia

Location

Related Publications (1)

• 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.

  PMID: 40598566 DERIVED

Study Officials

• Mark Shilkrut, MD

  Olema Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: August 10, 2020
• Study Start: August 13, 2020
• Primary Completion: July 30, 2024
• Study Completion: July 30, 2024
• Last Updated: August 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); AU (4)