Study of IEV407 as Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer

Purpose

The purpose of this study is to evaluate the safety, tolerability and preliminary activity of IEV407 as a single agent and in combination with endocrine therapy (fulvestrant or letrozole) in patients with advanced hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-negative) breast cancer.

Condition

  • Advanced HR+/HER2- Breast Cancer

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age ≥ 18 years old - Patients with one of the following indications: - Dose escalation (IEV407 single agent and in combination with fulvestrant or letrozole): HR+/HER2- aBC with disease progression on or following, or have been intolerant to, at least one line of endocrine-based therapy in combination with a CDK4/6 inhibitor and at least one additional line of systemic therapy in the unresectable/metastatic setting and not be a candidate for any available standard therapy, in the investigator's judgement. - Dose expansion of IEV407 in combination with fulvestrant: HR+/HER2- aBC with disease progression on or following, or have been intolerant to, endocrine-based therapy in combination with a CDK4/6 inhibitor. They must not have received more than two prior lines of endocrine-based therapy in the unresectable/metastatic setting. Prior cytotoxic chemotherapy and/or antibody-drug conjugate therapies in the unresectable/metastatic setting are not allowed.

Exclusion Criteria

  • Patients with inadequate bone marrow and/or organ functions with out-of-range laboratory values. - Impaired cardiac function or clinically significant cardiac disease. - Concurrent use of hormone replacement therapy. - Women of childbearing potential who are unwilling to use highly effective contraception methods, pregnant or nursing women. - For the combination treatment of IEV407 with fulvestrant or letrozole: Patients with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine-based therapy. Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose escalation: IEV407 single agent 		IEV407 single agent
  • Drug: IEV407
    Oral administration
Experimental
Dose escalation: IEV407 + fulvestrant 		IEV407 in combination with fulvestrant
  • Drug: IEV407
    Oral administration
  • Drug: Fulvestrant
    Intramuscular injection. Approved medication.
    Other names:
    • Faslodex
Experimental
Dose escalation: IEV407 + letrozole 		IEV407 in combination with letrozole
  • Drug: IEV407
    Oral administration
  • Drug: Letrozole
    Oral administration. Approved medication.
    Other names:
    • Femara
Experimental
Dose expansion, recommended dose (RD)-1: IEV407 + fulvestrant 		IEV407 in combination with fulvestrant
  • Drug: IEV407
    Oral administration
  • Drug: Fulvestrant
    Intramuscular injection. Approved medication.
    Other names:
    • Faslodex
Experimental
Dose expansion, RD-2 (optional dose optimization): IEV407 + fulvestrant 		IEV407 in combination with fulvestrant
  • Drug: IEV407
    Oral administration
  • Drug: Fulvestrant
    Intramuscular injection. Approved medication.
    Other names:
    • Faslodex

Recruiting Locations

Mary Crowley Cancer Research
Dallas, Texas 75251
Contact:
Pramitha Kondancheri
972-566-3000
Pramitha.RarothKondancheri@scri.com

More Details

Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

Detailed Description

This is a first-in-human, open-label, phase I/Ib, multi-center study consisting of a dose escalation part of IEV407 as a single agent (SA) and in combination with endocrine therapy (fulvestrant or letrozole) followed by a dose expansion part in patients with advanced breast cancer (aBC). The study will start with the evaluation of IEV407 as a SA. Following evaluation of IEV407 in combination with fulvestrant through dose escalation and establishment of a recommended dose and/or dose ranges for optimization (RD/DRO), the study may proceed to the Phase Ib expansion part to evaluate the combination treatment of IEV407 with fulvestrant. If more than one treatment arm is open concurrently in the dose expansion part, a randomization schedule will be employed for patient allocation.