Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer, ER Positive Breast Cancer, HER2 Negative Breast Carcinoma
Conditions
Brief summary
This phase 3 clinical trial compares the safety and efficacy of palazestrant (OP-1250) to the standard-of-care options of fulvestrant or an aromatase inhibitor in women and men with breast cancer whose disease has advanced on one endocrine therapy in combination with a CDK4/6 inhibitor.
Detailed description
This is an international, multicenter, randomized, open-label, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the safety and efficacy of palazestrant (OP-1250) as a single agent to the standard of care endocrine therapy: either fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane). This trial is seeking adult participants with ER+, HER2- advanced or metastatic breast cancer whose disease has relapsed or progressed on 1 or 2 prior lines of standard-of-care endocrine therapy for metastatic breast cancer. Prior lines of therapy must include one line of endocrine therapy in combination with a CDK 4/6 inhibitor. In the dose-selection part of the trial, approximately 120 participants will be randomized to one of the two doses of palazestrant or to the standard-of-care endocrine therapy. Thereafter, approximately 390 participants will be randomized to palazestrant at the selected dose or to the standard-of-care endocrine therapy.
Interventions
DRUGPalazestrant
Participants will be treated with palazestrant once daily on a 4 week (28 day) cycle. Doses evaluated in the dose-selection part will be 120 mg once daily and 90 mg once daily.
DRUGFulvestrant
Participants will be treated with fulvestrant on C1D1, C1D15, and then on Day 1 of every subsequent 4 week (28 day) cycle
DRUGAnastrozole
Participants will be treated with anastrozole once daily on a 4 week (28 day) cycle
DRUGLetrozole
Participants will be treated with letrozole once daily on a 4 week (28 day) cycle
DRUGExemestane
Participants will be treated with exemestane once daily on a 4 week (28 day) cycle
Sponsors
Olema Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: * Adult female or male participants. * ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy. * Evaluable disease (measurable disease or bone-only disease). * Previously received a CDK4/6 inhibitor in combination with an endocrine therapy in the advanced setting. One additional line of ET as a monotherapy is allowed. Duration of the most recent prior ET must be at least 6 months. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate hematologic, hepatic, and renal functions. * Female participants can be pre-, peri- or postmenopausal. * Male and pre- or peri-menopausal female participants must be willing to take a GnRH (or LHRH) agonist. Key
Exclusion criteria
* Symptomatic visceral disease, imminent organ failure, or any other reason that makes the participant ineligible for endocrine monotherapy. * Previously received chemotherapy in the advanced/metastatic setting. * Previously received treatment with elacestrant or an investigational estrogen receptor-directed therapy. * History of allergic reactions to study treatment. * Any contraindications to the selected standard-of-care endocrine therapy in the local prescribing information. * Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment. * Clinically significant comorbidities such as significant cardiac or cerebrovascular disease, gastrointestinal disorders that could affect absorption of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Selection Part: Incidence of adverse events | From Date of Randomization up to 16 weeks | To evaluate the number of participants with adverse events |
| Dose-Selection Part: Incidence of dose reduction | From Date of Randomization up to 16 weeks | To evaluate the number of participants reducing the dose of palazestrant |
| Dose-Selection Part: Incidence of drug discontinuation | From Date of Randomization up to 16 weeks | To evaluate the number of participants discontinuing palazestrant |
| Trial: Progression-Free Survival (PFS) | From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years) | To compare PFS, based on a Blinded Independent Review Committee (BIRC) assessment, between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1-mutation detected and ESR1-mutation not detected participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trial: Overall Survival (OS) | From Date of Randomization until Death Due to Any Cause (estimated as up to 4 years) | To compare OS between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1 mutation detected and ESR1 mutation not detected participants. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, France, Germany, Hong Kong, Hungary, Italy, Malaysia, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Romania, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
CONTACTOlema Pharmaceuticals, Inc.
STUDY_DIRECTORMedical Director, MD
Olema Pharmaceuticals, Inc.
Outcome results
None listed