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

Phase 1RecruitingNCT07604571

Novartis Pharmaceuticals194 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

194

Conditions

Advanced HR+/HER2- Breast Cancer

Interventions

IEV407DRUG

Oral administration

FulvestrantDRUG

Intramuscular injection. Approved medication.

LetrozoleDRUG

Oral administration. Approved medication.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (6)

Yale New Haven Hospital

New Haven, Connecticut, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, United States

RECRUITING

Novartis Investigative Site

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Incidence and severity of dose-limiting toxicities (DLTs)

Number of participants with DLTs. A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher, including death, unless clearly and incontrovertibly assessed as due to disease, disease progression, inter-current illness/injury, concomitant medications, or extraneous causes, that occurs within the first 28 days of treatment with IEV407 in the dose escalation parts or in the expansion part of IEV407 in combination with fulvestrant with the exceptions described in the study protocol.

Time frame: 28 days

Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of participants with AEs and SAEs, including changes in laboratory values, vital signs and echocardiograms (ECGs) qualifying and reported as AEs.

Time frame: Up to approximately 2 years

Frequency of dose interruptions, reductions and discontinuations

Number of participants with dose adjustments (interruptions, reductions, or permanent discontinuation) as a measure of tolerability.

Time frame: Up to approximately 2 years

Dose intensity

Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.

Time frame: Up to approximately 2 years

Secondary Outcomes

Best Overall Response (BOR)

BOR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) is defined as the best overall confirmed response recorded from the start of the treatment until progressive disease (PD), death, start of new therapy, withdrawal of consent or end of study, whatever comes first. Efficacy will be based on the investigator assessment.

Time frame: Up to approximately 2 years

Central Contacts

Novartis Pharmaceuticals

CONTACT

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

Novartis Pharmaceuticals

CONTACT

+41613241111

Data from ClinicalTrials.gov

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