Clinical trial NCT06726148: Study of ECI830 Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer and Other Advanced Solid Tumors
Official title: An Open-label, Multi-center, Phase I/II Study of ECI830 as a Single Agent and in Combination With Ribociclib and Endocrine Therapy in Patients With Advanced Hormone Receptor Positive, HER2-negative Breast Cancer and Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced HR+/HER2- Breast Cancer
Advanced CCNE1-amplified Solid Tumors
Keywords: ECI830
Ribociclib
Fulvestrant
Breast cancer
CCNE1 amplification
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-12-10
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase I: Characterize safety and tolerability of ECI830 as a single agent and in combination with ribociclib and fulvestrant. Identify dose range for optimization/recommended dose for future studies.

Phase II: Assess the anti-tumor activity of ECI830 in combination with ribociclib and fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer.

Detailed description: This is a first-in-human, open-label, phase I/II, multi-center study consisting of an ECI830 single agent treatment arm in patients with advanced HR+/HER2- breast cancer or other advanced solid tumors harboring CCNE1 amplification and a combination treatment arm of ECI830 with ribociclib and fulvestrant in patients with advanced breast cancer. Single agent escalation may be followed by an expansion part stratified by disease indication. The escalation of the combination arm may continue into a randomized, open label, Phase II with optional dose optimization in advanced breast cancer patients.

Eligibility criteria: Inclusion Criteria:

Age ≥ 18 years old.

Patients with one of the following indications:

Phase I:

HR+/HER2- aBC with disease progression on or following at least one line of hormone-based therapy in combination with a CDK4/6i and at least one additional line of systemic therapy for metastatic disease.

Histologically and/or cytologically confirmed diagnosis of locally advanced or metastatic cancer with a CCNE1 amplification. For dose expansion only: no more than 3 prior lines of therapy for advanced or metastatic disease.

Phase II:

HR+/HER2- aBC with disease progression on an aromatase inhibitor or tamoxifen in combination with a CDK4/6 inhibitor for unresectable/metastatic disease with no more than 2 lines of endocrine therapy.

Measurable disease as determined by RECIST v1.1.

BC only: If no measurable disease is present, then at least one predominantly lytic bone lesion must be present that can be accurately assessed at baseline and is suitable for repeated assessment.

Exclusion Criteria:

Previous treatment with a CDK2 inhibitor at any time.

Patients with inadequate bone marrow and/or organ functions with out-of-range laboratory values.

Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including MI, CABG, long QT syndrome, or risk factors for TdP.

Presence of symptomatic CNS metastases or CNS metastases that require local therapy or increasing doses of corticosteroids within 2 weeks prior to study entry.

For the combination treatment:

Patients with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine-based therapy.

Patients who could not tolerate the prescribed dose of ribociclib during a previous course of treatment, requiring dose reduction or permanent discontinuation due to adverse events.

For patients with BC: Patient is concurrently using hormone replacement therapy.

WOCBP who are unwilling to use highly effective contraception methods, pregnant or nursing women.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Phase I: Incidence of dose-limiting toxicities (DLTs)
timeFrame: 2 years
measure: Phase I: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 2 years
measure: Phase I: Number of participants with dose interruptions, reductions and discontinuations
timeFrame: 2 years
measure: Phase II: PFS rate at 6 months per local response evaluation criteria in solid tumors (RECIST) v1.1
timeFrame: 6 months
Secondary outcomes:
measure: Phase I and II: Area under the plasma concentration-time curve (AUC) of ECI830 and ribociclib
timeFrame: From pre-dose up to 24 hours post-dose in Cycle 1. One cycle=28 days.
measure: Phase I and II: Maximum observed plasma concentration (Cmax) of ECI830 and ribociclib
timeFrame: From pre-dose up to 24 hours post-dose in Cycle 1. One cycle=28 days.
measure: Phase I and II: Best overall response (BOR) per RECIST v1.1
timeFrame: 2 years
measure: Phase I and II: Overall response rate (ORR) per RECIST v1.1
timeFrame: 2 years
measure: Phase I and II: Disease control rate (DCR) per RECIST v1.1
timeFrame: 2 years
measure: Phase I and II: Clinical benefit rate (CBR) per RECIST v1.1
timeFrame: 2 years
measure: Phase I and II: Progression Free Survival (PFS) per RECIST v1.1
timeFrame: 2 years
measure: Phase II: Duration of Response (DOR) per RECIST v1.1
timeFrame: 2 years
measure: Phase II: Overall Survival (OS)
timeFrame: 2 years
measure: Phase II: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 2 years
measure: Phase II: Number of participants with dose interruptions, reductions and discontinuations
timeFrame: 2 years
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
References: