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

An Open-label, Multi-center, Phase I/Ib Study of IEV407 as a Single Agent and in Combination With Endocrine Therapy in Patients With Advanced Hormone Receptor Positive, HER2- Negative Breast Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced HR+/HER2- Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Letrozole; Drug: IEV407

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.

• Study Type: Interventional
• Enrollment (Estimated): 194
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation: IEV407 single agent; IEV407 single agent	Drug: IEV407; Oral administration
Experimental: Dose escalation: IEV407 + fulvestrant; IEV407 in combination with fulvestrant	Drug: Fulvestrant; Intramuscular injection. Approved medication.; Other Names: Faslodex; Drug: IEV407; Oral administration
Experimental: Dose escalation: IEV407 + letrozole; IEV407 in combination with letrozole	Drug: Letrozole; Oral administration. Approved medication.; Other Names: Femara; Drug: IEV407; Oral administration
Experimental: Dose expansion, recommended dose (RD)-1: IEV407 + fulvestrant; IEV407 in combination with fulvestrant	Drug: Fulvestrant; Intramuscular injection. Approved medication.; Other Names: Faslodex; Drug: IEV407; Oral administration
Experimental: Dose expansion, RD-2 (optional dose optimization): IEV407 + fulvestrant; IEV407 in combination with fulvestrant	Drug: Fulvestrant; Intramuscular injection. Approved medication.; Other Names: Faslodex; Drug: IEV407; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Up to approximately 2 years
Dose intensity	Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 2 years
Overall Response Rate (ORR)	ORR per RECIST v1.1 is defined as the proportion of patients with a BOR of Complete response (CR) or Partial response (PR). Efficacy will be based on the investigator assessment.	Up to approximately 2 years
Disease Control Rate (DCR)	DCR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or Stable Disease (SD). Efficacy will be based on the investigator assessment.	Up to approximately 2 years
Clinical Benefit Rate (CBR)	CBR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or an overall lesion response of SD or Non-CR/Non-PD which lasts for at least 24 weeks. Efficacy will be based on the investigator assessment.	Up to approximately 2 years
Duration of Response (DOR)	DOR per RECIST v1.1 is the time between the first documented response (CR or PR) and the date of progression by local review as applicable or death due to any cause. Efficacy will be based on the investigator assessment.	Up to approximately 2 years
Progression Free Survival (PFS)	PFS per RECIST 1.1 is defined as the time from the date of start of study treatment (Phase I) or the date of randomization (Phase II) to the date of the first documented progression or death due to any cause. Efficacy will be based on the investigator assessment.	Up to approximately 2 years
Maximum plasma concentration (Cmax) of IEV407	Pharmacokinetic (PK) parameters based on plasma concentrations of IEV407.	From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days
Area under the plasma concentration-time curve (AUC) of IEV407	PK parameters based on plasma concentrations of IEV407.	From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 12, 2026
• Primary Completion (Estimated): June 8, 2032
• Study Completion (Estimated): June 8, 2032

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: letrozole; fulvestrant; HR+/HER2- advanced breast cancer; IEV407
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Letrozole; Fulvestrant
• Other Study ID Numbers: CIEV407A12101; 2025-522707-26 (Registry Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No