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
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Beräknad)
Fas
- Fas 1
Kontakter och platser
Studiekontakt
- Namn: Novartis Pharmaceuticals
- Telefonnummer: 1-888-669-6682
- E-post: novartis.email@novartis.com
Studera Kontakt Backup
- Namn: Novartis Pharmaceuticals
- Telefonnummer: +41613241111
Studieorter
-
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Connecticut
-
New Haven, Connecticut, Förenta staterna, 06520
- Rekrytering
- Yale New Haven Hospital
-
Kontakt:
- Carl Brown
- E-post: carl.brown@yale.edu
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Huvudutredare:
- Jing Du
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Texas
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Dallas, Texas, Förenta staterna, 75251
- Rekrytering
- Mary Crowley Cancer Research
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Huvudutredare:
- Reva Schneider
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Kontakt:
- Pramitha Kondancheri
- Telefonnummer: +1 972 566 3000
- E-post: Pramitha.RarothKondancheri@scri.com
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Osaka
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Hirakata, Osaka, Japan, 5731191
- Rekrytering
- Novartis Investigative Site
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-
-
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Ontario
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Toronto, Ontario, Kanada, M5G 2M9
- Rekrytering
- Novartis Investigative Site
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Singapore, Singapore, 119074
- Rekrytering
- Novartis Investigative Site
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Seoul
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Seoul, Seoul, Sydkorea, 06351
- Rekrytering
- Novartis Investigative Site
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Beskrivning
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.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Sekventiell tilldelning
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Dose escalation: IEV407 single agent
IEV407 single agent
|
Oral administration
|
|
Experimentell: Dose escalation: IEV407 + fulvestrant
IEV407 in combination with fulvestrant
|
Intramuscular injection.
Approved medication.
Andra namn:
Oral administration
|
|
Experimentell: Dose escalation: IEV407 + letrozole
IEV407 in combination with letrozole
|
Oral administration.
Approved medication.
Andra namn:
Oral administration
|
|
Experimentell: Dose expansion, recommended dose (RD)-1: IEV407 + fulvestrant
IEV407 in combination with fulvestrant
|
Intramuscular injection.
Approved medication.
Andra namn:
Oral administration
|
|
Experimentell: Dose expansion, RD-2 (optional dose optimization): IEV407 + fulvestrant
IEV407 in combination with fulvestrant
|
Intramuscular injection.
Approved medication.
Andra namn:
Oral administration
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Incidence and severity of dose-limiting toxicities (DLTs)
Tidsram: 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.
|
28 days
|
|
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsram: 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.
|
Up to approximately 2 years
|
|
Frequency of dose interruptions, reductions and discontinuations
Tidsram: Up to approximately 2 years
|
Number of participants with dose adjustments (interruptions, reductions, or permanent discontinuation) as a measure of tolerability.
|
Up to approximately 2 years
|
|
Dose intensity
Tidsram: Up to approximately 2 years
|
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
|
Up to approximately 2 years
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Best Overall Response (BOR)
Tidsram: 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.
|
Up to approximately 2 years
|
|
Overall Response Rate (ORR)
Tidsram: 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. |
Up to approximately 2 years
|
|
Disease Control Rate (DCR)
Tidsram: 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. |
Up to approximately 2 years
|
|
Clinical Benefit Rate (CBR)
Tidsram: 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. |
Up to approximately 2 years
|
|
Duration of Response (DOR)
Tidsram: 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. |
Up to approximately 2 years
|
|
Progression Free Survival (PFS)
Tidsram: 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. |
Up to approximately 2 years
|
|
Maximum plasma concentration (Cmax) of IEV407
Tidsram: 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.
|
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
Tidsram: 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.
|
From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days
|
Samarbetspartners och utredare
Sponsor
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Hormoner
- Hormoner, hormonsubstitut och hormonantagonister
- Organiska kemikalier
- Heterocykliska föreningar, 1-ring
- Heterocykliska föreningar
- Azoler
- Polycykliska föreningar
- Steroider
- Fusion-ringföreningar
- Nitriler
- Östradiol
- Estren
- Östran
- Östradiolkongener
- Gonadal steroidhormoner
- Gonadalhormoner
- Triazoler
- Letrozol
- Fulvestrant
Andra studie-ID-nummer
- CIEV407A12101
- 2025 (U.S.S. NIH-anslag/kontrakt: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
- 2025-522707-26 (Registeridentifierare: EU CTIS)
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