ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer
Phase 1
Active, not recruiting
- Conditions
- Breast Cancer
- Interventions
- Drug: ARV-471 in combination with Everolimus
- Registration Number
- NCT05501769
- Lead Sponsor
- Arvinas Estrogen Receptor, Inc.
- Brief Summary
A phase 1b study to assess the combination of ARV-471 and everolimus in participants with advanced or metastatic ER+/HER2- breast cancer.
- Detailed Description
This is a Phase 1b study to assess the safety and tolerability of ARV-471 in combination with everolimus in participants with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer, who have received a prior CDK4/6 inhibitor and endocrine therapy in the advanced/metastatic setting.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 32
Inclusion Criteria
- Histologically or cytologically confirmed ER+ and HER2-advanced breast cancer (metastatic, recurrent, or unresectable)
- Women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression
- Measurable disease or non-measurable (evaluable) disease per RECIST v1.1
- Received a minimum of 1 and up to 3 lines of anti-cancer therapy in the advanced/metastatic setting: must have received and progressed on (or were intolerant to) a CDK 4/6 inhibitor, either alone or in combination; must have received at least one endocrine therapy, either alone or in combination; may have received up to one line of chemotherapy
- Must be willing to use dexamethasone mouthwash for the prevention of everolimus-induced stomatitis
- ECOG performance status of 0 or 1
Exclusion Criteria
- Untreated brain metastases or brain metastases requiring steroids above physiologic replacement doses
- Prior treatment with ARV-471
- Prior treatment targeting mTOR (e.g. everolimus)
- Prior anticancer or investigational drug treatment within 28 days (fulvestrant) or 14 days (tamoxifen or aromatase inhibitor, or CDK 4/6 inhibitor) before the first dose of study drug
- Prior anticancer or investigational anticancer drug therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of study drug, except as mentioned above
- Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolism
- Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, sustained ventricular tachyarrhythmia and ventricular fibrillation, left anterior hemiblock, ongoing cardiac arrythmias/dysrhythmias, atrial fibrillation
- Hypertension that cannot be controlled by medication (>150/90 mmHg despite optimal medical therapy)
- Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
- Known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung function
- Live vaccines within 14 days before the first dose of study drug
- Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug
- Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to more than 25% of the bone marrow
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ARV-471 and Everolimus ARV-471 in combination with Everolimus ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles
- Primary Outcome Measures
Name Time Method Incidence of dose limiting toxicities of ARV-471 in combination with everolimus 35 Days Dose limiting toxicities in the first 35 days of the study combination treatment characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study drug
Recommended Phase 2 Dose (RP2D) for ARV-471 in combination with everolimus 35 Days Number of participants with adverse events as a measure of safety and tolerability of ARV-471 in combination with everolimus 28 calendar days after participant discontinues study treatment Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination
Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471 in combination with everolimus 28 calendar days after participant discontinues study treatment Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing
- Secondary Outcome Measures
Name Time Method Maximum plasma concentrations (Cmax) of ARV-471 and everolimus At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products Duration of response (DOR) in participants Up to approximately 1 year Overall response rate (ORR) in participants Up to approximately 1 year Clinical benefit rate (CBR) in participants. Up to approximately 1 year Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer.
Time to maximum plasma concentrations (Tmax) of ARV-471 and everolimus At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products Area under the concentration-time curve over 24 hours at steady state (AUC(0-24)) of ARV-471 and everolimus At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
Trial Locations
- Locations (1)
Clinical Trial Site
🇪🇸Valencia, Spain