Clinical trial NCT04505826: A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hormone Receptor Positive Breast Carcinoma
HER2-negative Breast Cancer
Lead sponsor: Olema Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-10
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: The first 28 days of treatment
measure: Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250
timeFrame: Up to 42 days after end of treatment
measure: Pharmacokinetics of OP-1250
timeFrame: Every 28 days
measure: Anti-tumor activity of OP-1250
timeFrame: Every 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Deerfield Beach
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer Center
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Sydney
country: Australia
facility: Macquarie University
state: New South Wales
city: Westmead
country: Australia
facility: Westmead
state: New South Wales
city: Auchenflower
country: Australia
facility: ICON Cancer Centre
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research South Australia
state: South Australia
Study officials:
affiliation: Olema Pharmaceuticals, Inc.
name: Mark Shilkrut, MD
role: STUDY_DIRECTOR
affiliation: Olema Pharmaceuticals, Inc.
name: Gurpreet Mathauda-Sahota, PharmD
role: STUDY_DIRECTOR
References: