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.
Brief Title
A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hormone Receptor Positive Breast Carcinoma
HER2-negative Breast Cancer
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04505826
Org Class
Industry
Org Full Name
Olema Pharmaceuticals, Inc.
Org Study Id
OP-1250-001
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of OP-1250, the incidence of DLTs will be assessed.
Outcome Measure
Dose Limiting Toxicities (DLT)
Outcome Time Frame
The first 28 days of treatment
Outcome Description
Characterize the incidence, nature and severity of TEAEs and SAEs of OP-1250 according to NCI-CTCAE version 5.0
Outcome Measure
Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250
Outcome Time Frame
Up to 42 days after end of treatment
Outcome Description
Plasma concentrations of OP-1250 will be assessed at predefined intervals
Outcome Measure
Pharmacokinetics of OP-1250
Outcome Time Frame
Every 28 days
Outcome Description
Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines
Outcome Measure
Anti-tumor activity of OP-1250
Outcome Time Frame
Every 8 weeks
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Della Makower
Investigator Email
DMAKOWER@montefiore.org