Advanced HR+/HER2- Breast Cancer
Conditions
Keywords
IEV407, HR+/HER2- advanced breast cancer, letrozole, fulvestrant
Brief 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 cancer.
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.
Interventions
DRUGIEV407
Oral administration
DRUGFulvestrant
Intramuscular injection. Approved medication.
DRUGLetrozole
Oral administration. Approved medication.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of dose-limiting toxicities (DLTs) | 28 days | 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. |
| Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 2 years | Number of participants with AEs and SAEs, including changes in laboratory values, vital signs and echocardiograms (ECGs) qualifying and reported as AEs. |
| Frequency of dose interruptions, reductions and discontinuations | Up to approximately 2 years | Number of participants with dose adjustments (interruptions, reductions, or permanent discontinuation) as a measure of tolerability. |
| Dose intensity | Up to approximately 2 years | Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) | Up to approximately 2 years | 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. |
| Overall Response Rate (ORR) | Up to approximately 2 years | 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. |
| Disease Control Rate (DCR) | Up to approximately 2 years | 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. |
| Clinical Benefit Rate (CBR) | Up to approximately 2 years | 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. |
| Duration of Response (DOR) | Up to approximately 2 years | 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. |
| Progression Free Survival (PFS) | Up to approximately 2 years | 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. |
| Maximum plasma concentration (Cmax) of IEV407 | From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days | Pharmacokinetic (PK) parameters based on plasma concentrations of IEV407. |
| Area under the plasma concentration-time curve (AUC) of IEV407 | From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days | PK parameters based on plasma concentrations of IEV407. |
Countries
Canada, Japan, Singapore, South Korea, United States
Contacts
CONTACTNovartis Pharmaceuticals
Outcome results
None listed