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

HER2-negative Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04505826
• Other study ID #: OP-1250-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 13, 2020
• Est. completion date: July 2024

Study information

• Verified date: August 2023
• Source: Olema Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 153
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-negative Breast Cancer
• Hormone Receptor Positive Breast Carcinoma

Intervention

Drug:
• OP-1250
Complete Estrogen Receptor ANtagonist (CERAN)

Locations

Country	Name	City	State
Australia	Cancer Research South Australia	Adelaide	South Australia
Australia	ICON Cancer Centre	Auchenflower	Queensland
Australia	Macquarie University	Sydney	New South Wales
Australia	Westmead	Westmead	New South Wales
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	University of Miami, Sylvester Comprehensive Cancer Center	Deerfield Beach	Florida
United States	Indiana University Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	UCLA Hematology/Oncology	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Advent Health	Orlando	Florida
United States	OHSU Knight Cancer Institute	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Florida Cancer Center	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Olema Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Pharmacokinetics of OP-1250	Plasma concentrations of OP-1250 will be assessed at predefined intervals	Every 28 days
Primary	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