ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer

Breast Cancer Clinical Trial

— TACTIVE-E  

Official title:

A Phase 1b Trial of ARV-471 in Combination With Everolimus in Patients With ER+, HER2- Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05501769
• Other study ID #: ARV-471-mBC-102
• Secondary ID: C4891020
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 8, 2022
• Est. completion date: November 30, 2024

Study information

• Verified date: January 2024
• Source: Arvinas Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 1b study to assess the combination of ARV-471 and everolimus in participants with advanced or metastatic ER+/HER2- breast cancer.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: November 30, 2024
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• ARV-471 in combination with Everolimus
ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles

Locations

Country	Name	City	State
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Valencia
United States	Clinical Trial Site	Ann Arbor	Michigan
United States	Clinical Trial Site	Lake Mary	Florida
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	San Diego	California
United States	Clinical Trial Site	Santa Monica	California
United States	Clinical Trial Site	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Arvinas Estrogen Receptor, Inc.	Pfizer

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities of ARV-471 in combination with everolimus	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	35 Days
Primary	Recommended Phase 2 Dose (RP2D) for ARV-471 in combination with everolimus		35 Days
Primary	Number of participants with adverse events as a measure of safety and tolerability of ARV-471 in combination with everolimus	Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination	28 calendar days after participant discontinues study treatment
Primary	Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471 in combination with everolimus	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing	28 calendar days after participant discontinues study treatment
Secondary	Overall response rate (ORR) in participants		Up to approximately 1 year
Secondary	Clinical benefit rate (CBR) in participants.	Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer.	Up to approximately 1 year
Secondary	Duration of response (DOR) in participants		Up to approximately 1 year
Secondary	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
Secondary	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
Secondary	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