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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arvinas Estrogen Receptor Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Mar 2023 → 26 Aug 2025

Decision date (initial)

2024-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Arvinas Estrogen Receptor, Inc.

External identifiers

EU CT number

2024-513284-30-00

EudraCT number

2021-003047-14

ClinicalTrials.gov

NCT05501769

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety

Evaluate the safety and tolerability of ARV-471 in combination with everolimus and select the RP2D for the combination.

Secondary objectives 3

1. Assess preliminary anti-tumor activity of ARV-471 in combination with everolimus.
2. Characterize the PK of ARV-471 in combination with everolimus.
3. Characterize the PK of everolimus when given alone and in combination with ARV-471.

Conditions and MedDRA coding

ER+, HER2– Advanced or Metastatic Breast Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients must be ≥ 18 years.
2. Patients must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer (metastatic, recurrent, or unresectable). • ER+ disease must be documented by IHC according to the ASCO/CAP Guidelines • HER2- disease must be documented by either IHC or in situ hybridization per ASCO/CAP guidelines
3. Women must meet definitions below for one of the following categories: Postmenopausal women must have at least 1 of the following: prior bilateral oophorectomy, age ≥ 60 years, or age < 60 years and amenorrheic for at least 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH/estradiol in the postmenopausal range • Pre- and peri-menopausal women must be on ovarian suppression with a GnRH agonist for at least 4 weeks prior to initiation of study treatment and for 8 weeks after the last dose of study treatment.
4. Patients must have measurable disease or non-measurable (evaluable) disease, per RECIST 1.1.
5. ECOG (Eastern Cooperative Group) performance status of 0 or 1.
6. Patients must have received a minimum of 1 and up to 3 lines of anticancer therapy in the advanced/metastatic setting: • Patients must have received and progressed on (or were intolerant to) a CDK 4/6 inhibitor, either alone or in combination • Patients must have received at least 1 endocrine therapy, either alone or in combination • Patients may have received up to 1 line of chemotherapy
7. Must be willing and capable of taking oral medication without crushing, dissolving, or chewing tablets/capsules.

Exclusion criteria 9

1. Untreated brain metastases or brain metastases requiring steroids above physiologic replacement doses
2. Any of the following in the previous 12 months: • Myocardial infarction • Severe/unstable angina • Coronary/peripheral artery bypass graft • Symptomatic (NYHA class III or IV) congestive heart failure • Cerebrovascular accident (CVA) • Transient ischemic attack (TIA) • Symptomatic pulmonary embolism • Other clinically significant episode of thromboembolism
3. 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 (bifascicular block) • Ongoing cardiac arrythmias/dysrhythmias of NCI CTCAE Grade ≥2 • Atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation)
4. Patients with a known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung function.
5. Prior treatment with ARV-471.
6. Prior treatment(s) (including investigational treatments) targeting mTOR (e. g. everolimus).
7. Prior anticancer or investigational drug treatment within the following windows: • Fulvestrant treatment < 28 days before C1D1 • Tamoxifen or AI < 14 days before C1D1 • CDK 4/6 treatment < 14 days before C1D1
8. Any prior anticancer or investigational anticancer drug therapy < 28 days or five half-lives (whichever is shorter) before C1D1 (except as mentioned in exclusion criteria above).
9. Any live vaccines within 14 days of C1D1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. First-cycle DLTs and determination of a RP2D.
2. Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination.
3. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Secondary endpoints 4

1. ORR by Investigator per RECIST v1.1 in patients with measurable disease at baseline.
2. CBR by Investigator (includes all CRs, all PRs, and SD lasting at least 24 weeks).
3. DOR.
4. PK parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arvinas Estrogen Receptor Inc.

Sponsor organisation

Arvinas Estrogen Receptor Inc.

Address

5 Science Park

City

New Haven

Postcode

06511-1966

Country

United States

Scientific contact point

Organisation

Arvinas Estrogen Receptor Inc.

Contact name

Susan Ivie

Public contact point

Organisation

Arvinas Estrogen Receptor Inc.

Contact name

Suzette Dowling

Third parties 8

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications