Advanced HR+/HER2- Breast CancerPhase 1NCT07604571
Study of IEV407 as Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer
A Phase 1 study testing IEV407, Fulvestrant and Letrozole in people with Advanced HR+/HER2- Breast Cancer, run by Novartis Pharmaceuticals at 10 sites in 7 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced HR+/HER2- Breast Cancer
- What is being tested?
- IEV407, Fulvestrant and Letrozole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 194 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 28 May 2026to 8 Jun 2032
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
10 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
10 sites in 7 countries
United States3 sites, 3 recruiting
- Recruiting
Mary Crowley Cancer Research
Dallas, Texas, 75251
Pramitha Kondancheri, +1 972 566 3000, Pramitha.RarothKondancheri@scri.com
Reva Schneider
- Recruiting
Univ of Kansas Hosp and Med Ctr
Kansas City, Kansas, 66160
LeAnn Nguyen, +1 913 588 2566, lnguyen14@kumc.edu
Anne O Dea
- Recruiting
Yale New Haven Hospital
New Haven, Connecticut, 06520
Carl Brown, carl.brown@yale.edu
Jing Du
France2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Marseille, 13273
- Recruiting
Novartis Investigative Site
Toulouse, 31059
Canada1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Italy1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Ancona, AN, 60020
Japan1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Hirakata, Osaka, 5731191
Singapore1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Singapore, 119074
South Korea1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Seoul, Seoul, 06351
About this study
Official title: 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.
Read the 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.
- Conditions
- Advanced HR+/HER2- Breast Cancer
- Being tested
- IEV407, Fulvestrant, Letrozole
- Keywords
- IEV407, HR+/HER2- advanced breast cancer, letrozole, fulvestrant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IEV407Drug
Oral administration
FulvestrantDrug
Also called Faslodex
Intramuscular injection. Approved medication.
LetrozoleDrug
Also called Femara
Oral administration. Approved medication.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation: IEV407 single agent | Experimental | IEV407 single agent Receives: Drug: IEV407 |
| Dose escalation: IEV407 + fulvestrant | Experimental | IEV407 in combination with fulvestrant Receives: Drug: IEV407; Drug: Fulvestrant |
| Dose escalation: IEV407 + letrozole | Experimental | IEV407 in combination with letrozole Receives: Drug: IEV407; Drug: Letrozole |
| Dose expansion, recommended dose (RD)-1: IEV407 + fulvestrant | Experimental | IEV407 in combination with fulvestrant Receives: Drug: IEV407; Drug: Fulvestrant |
| Dose expansion, RD-2 (optional dose optimization): IEV407 + fulvestrant | Experimental | IEV407 in combination with fulvestrant Receives: Drug: IEV407; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 2 years
Dose intensity
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
Measured: Up to approximately 2 years
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 2 years
Maximum plasma concentration (Cmax) of IEV407
Pharmacokinetic (PK) parameters based on plasma concentrations of IEV407.
Measured: 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.
Measured: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2026
- Study start28 May 2026
- Primary completion8 Jun 2032 (estimated)
- Study completion8 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced HR+/HER2- Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 194 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07604571
- Sponsor's protocol ID
- CIEV407A12101
- Other IDs
- 2025-522707-26, 2025
- Status last verified
- Oct 2026
- First submitted
- 18 May 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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/.