HER2-negative Breast Cancer, Hormone Receptor Positive Breast Carcinoma
Conditions
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. 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.
Interventions
DRUGOP-1250
Complete Estrogen Receptor ANtagonist (CERAN)
Sponsors
Olema Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 Key
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) | Up to 28 days from start of treatment | Number of Participants with Dose Limiting Toxicities (DLT) during Dose Escalation Only |
| Characterize the Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) of OP-1250 That Had at Least One Treatment Emergent Adverse Event | Up to 3 years, 11 months, and 17 days. | Characterize the incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250 in patients that had at least one treatment emergent adverse event according to NCI-CTCAE version 5.0. |
| Pharmacokinetics of OP-1250 | AUC (0-24) at steady state after 4 weeks of administration | Plasma concentrations of OP-1250 assessed steady state |
| Anti-tumor Activity of OP-1250 (cPR) | Imaging studies performed every 8 weeks from date of first dose through cycle 9 then afterwards every 12 weeks until date of first documented disease progression: assessed up to 3 years, 11 months, and 17 days | Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines (Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR)). Overall response rate which includes confirmed Partial Response (cPR). |
Countries
Australia, United States
Contacts
STUDY_DIRECTORMargaret Tonda
Olema Pharmaceuticals, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 99 Participants |
| Age, Continuous | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 127 Participants |
| Region of Enrollment Australia | 0 participants |
| Region of Enrollment United States | 134 participants |
| Sex: Female, Male Female | 152 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 5 | 5 / 33 | 1 / 6 | 5 / 83 | 1 / 5 | 1 / 7 | 1 / 7 | 2 / 7 |
| other Total, other adverse events | 5 / 5 | 29 / 33 | 5 / 6 | 79 / 83 | 5 / 5 | 7 / 7 | 7 / 7 | 6 / 7 |
| serious Total, serious adverse events | 0 / 5 | 4 / 33 | 2 / 6 | 16 / 83 | 2 / 5 | 2 / 7 | 2 / 7 | 4 / 7 |
Outcome results
None listed