Breast Cancer, Locally Advanced Breast Cancer, Metastatic Breast Cancer, ER Positive Breast Cancer, HER2 Negative Breast Carcinoma
Conditions
Keywords
Randomized, Multicenter, Double-Blind, Active-Controlled, Phase 3, Palazestrant, Complete Estrogen Receptor Antagonist (CERAN), Selective Estrogen Receptor Degrader (SERD), Ribociclib, CDK4/6i, Letrozole, Aromatase inhibitors, Antineoplastic agents
Brief summary
This phase 3 clinical trial compares the efficacy and safety of palazestrant with ribociclib to letrozole and ribociclib in women and men who have not received prior systemic anti-cancer treatment for advanced breast cancer.
Detailed description
This is an international, multicenter, randomized, double-blind, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the efficacy and safety of palazestrant in combination with ribociclib +letrozole -matching placebo (Arm A: investigational arm) with letrozole in combination with ribociclib + palazestrant-matching placebo (Arm B: control arm). This trial is seeking adult participants with ER+, HER2- advanced breast cancer who have not received prior systemic anti-cancer treatment for advanced disease. Approximately 1,000 participants will be randomized in a 1:1 ratio to one of the two study arms.
Interventions
DRUGPalazestrant
Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.
Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle
DRUGRibociclib
Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle.
DRUGLetrozole
Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle
DRUGPalazestrant matching-placebo
Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle
Sponsors
Olema Pharmaceuticals, Inc.
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 per RECIST 1.1 or bone-only disease). * De novo advanced breast cancer or with disease recurrence occurring after 12 months of completing adjuvant endocrine therapy (with or without CDK4/6 inhibitors) * 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.
Exclusion criteria
* Disease recurrence during adjuvant endocrine therapy * Currently receiving or previously received systemic anti-cancer therapy for ER+, HER2- advanced breast cancer. * Previously received treatment with fulvestrant, elacestrant or an investigational endocrine therapy in any setting. * History of allergic reactions to study treatment. * Any contraindications to letrozole and ribociclib. * Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years) | To compare PFS, based on a local investigator assessment, between investigational (palazestrant with ribociclib + letrozole-matching placebo) and control (letrozole with ribociclib + palazestrant-matching placebo) arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response Rate (ORR) | From Date of Randomization until Tumor Response (estimated as up to 3.5 years) | To evaluate ORR based on Blinded Independent Review Committee (BIRC) assessment |
| Overall Survival (OS) | From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years) | To compare OS between investigational and control arms. |
| Progression Free Survival (PFS) | From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years) | To evaluate PFS based on Blinded Independent Review Committee (BIRC) assessment |
| Clinical Benefit Rate (CBR) | Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years) | To evaluate CBR based on Blinded Independent Review Committee (BIRC) assessment |
| Safety and tolerability | Up to 42 days after end of treatment (estimated as up to 3.5 years) | To evaluate safety and tolerability assessed by AEs, SAEs, dose modifications, clinical laboratory parameters, ECGs, performance status and vital sign measurements |
| Pharmacokinetics (PK) of palazestrant and ribociclib | Every 28 days (estimated as up to 3.5 years) | To evaluate plasma levels of palazestrant and ribociclib to establish pharmacokinetic (PK) parameters |
| Duration of Response (DOR) | From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years) | To evaluate DOR based on Blinded Independent Review Committee (BIRC) assessment |
| Health-related patient-reported outcomes (PROs) | Every 28 days (estimated as up to 3.5 years) | To evaluate the change from baseline in health-related PROs assessed using standardized instruments that are widely used in (breast) cancer clinical trials |
Countries
Australia, Canada, Hong Kong, Malaysia, Netherlands, South Korea, Taiwan, Thailand, United Kingdom, United States
Contacts
CONTACTOlema Pharmaceuticals, Inc.
STUDY_DIRECTORMedical Director, MD
Olema Pharmaceuticals, Inc.
Outcome results
None listed