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

• Sponsor: Arvinas Estrogen Receptor, Inc. (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05501769
• Collaborator: Pfizer (Industry)
• Enrollment: 32
• Locations: 5
• Arm: 1
• Anticipated Duration (Months): 18
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: ARV-471 in combination with Everolimus	Phase 1

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Trial of ARV-471 in Combination With Everolimus in Patients With ER+, HER2- Advanced or Metastatic Breast Cancer
• Anticipated Study Start Date: Aug 1, 2022
• Anticipated Primary Completion Date: Aug 1, 2023
• Anticipated Study Completion Date: Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARV-471 and Everolimus ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles	Drug: ARV-471 in combination with Everolimus; ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles

Outcome Measures

Primary Outcome Measures

1. 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

2. Recommended Phase 2 Dose (RP2D) for ARV-471 in combination with everolimus [35 Days]

   Dose limiting toxicities in the first 35 days of the study combination will be assessed to determine the dose of ARV-471 and everolimus associated with acceptable safety and tolerability

3. 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

4. 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

1. Overall response rate (ORR) in participants [Up to approximately 1 year]

2. Clinical benefit rate (CBR) in participants [Up to approximately 1 year]

3. Duration of response (DOR) in participants [Up to approximately 1 year]

4. 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]

5. 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]

6. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	San Diego	California	United States	92037
2	Clinical Trial Site	Santa Monica	California	United States	90404
3	Clinical Trial Site	Lake Mary	Florida	United States	32746
4	Clinical Trial Site	Ann Arbor	Michigan	United States	48109
5	Clinical Trial Site	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• Arvinas Estrogen Receptor, Inc.
• Pfizer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Arvinas Estrogen Receptor, Inc.
• ClinicalTrials.gov Identifier: NCT05501769
• Other Study ID Numbers: ARV-471-mBC-102
• First Posted: Aug 15, 2022
• Last Update Posted: Aug 15, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Arvinas Estrogen Receptor, Inc.: Advanced breast cancer; Metastatic breast cancer; MBC; Endocrine therapy; Estrogen receptor; ER+; human epidermal growth factor receptor 2; HER2-; ARV-471; Everolimus
• Additional relevant MeSH terms: Breast Neoplasms; Everolimus

Study Results

No Results Posted as of Aug 15, 2022