Clinical trial NCT05501769: ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer
Official title: A Phase 1b Trial of ARV-471 in Combination With Everolimus in Patients With ER+, HER2- Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Keywords: Advanced breast cancer
Metastatic breast cancer
MBC
Endocrine therapy
Estrogen receptor
ER+
human epidermal growth factor receptor 2
HER2-
ARV-471
Everolimus
PROTAC
Vepdegestrant
Lead sponsor: Arvinas Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2022-08-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose limiting toxicities of ARV-471 in combination with everolimus
timeFrame: 35 Days
measure: Recommended Phase 2 Dose (RP2D) for ARV-471 in combination with everolimus
timeFrame: 35 Days
measure: Number of participants with adverse events as a measure of safety and tolerability of ARV-471 in combination with everolimus
timeFrame: 28 calendar days after participant discontinues study treatment
measure: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471 in combination with everolimus
timeFrame: 28 calendar days after participant discontinues study treatment
Secondary outcomes:
measure: Overall response rate (ORR) in participants
timeFrame: Up to approximately 1 year
measure: Clinical benefit rate (CBR) in participants.
timeFrame: Up to approximately 1 year
measure: Duration of response (DOR) in participants
timeFrame: Up to approximately 1 year
measure: Maximum plasma concentrations (Cmax) of ARV-471 and everolimus
timeFrame: At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
measure: Time to maximum plasma concentrations (Tmax) of ARV-471 and everolimus
timeFrame: At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
measure: Area under the concentration-time curve over 24 hours at steady state (AUC(0-24)) of ARV-471 and everolimus
timeFrame: At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Santa Monica
country: United States
facility: Clinical Trial Site
state: California
city: Washington
country: United States
facility: Clinical Trial Site
state: District of Columbia
city: Lake Mary
country: United States
facility: Clinical Trial Site
state: Florida
city: Ann Arbor
country: United States
facility: Clinical Trial Site
state: Michigan
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Valencia
country: Spain
facility: Clinical Trial Site
Study officials:
References: