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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hormone Receptor Positive Breast Carcinoma; HER2-negative Breast Cancer
• Intervention / Treatment: Drug: OP-1250

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial.; Phone Number: (415) 651-7206; Email: clinical@olema.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University
    • Westmead, New South Wales, Australia, 2145
      • Westmead
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Icon Cancer Centre
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research South Australia
• United States
  • California
    • Los Angeles, California, United States, 90404
      • UCLA Hematology/Oncology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami, Sylvester Comprehensive Cancer Center
    • Orlando, Florida, United States, 32804
      • Advent Health
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: OP-1250; Complete Estrogen Receptor ANtagonist (CERAN)
Experimental: 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.	Drug: OP-1250; Complete Estrogen Receptor ANtagonist (CERAN)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Olema Pharmaceuticals, Inc.
• Investigators: Study Director: Mark Shilkrut, MD, Olema Pharmaceuticals, Inc.; Study Director: Gurpreet Mathauda-Sahota, PharmD, Olema Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: August 6, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 20, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: OP-1250-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No