Study of ECI830 Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

Phase 2RecruitingNCT06726148

Novartis Pharmaceuticals280 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

280

Conditions

Advanced HR+/HER2- Breast Cancer Advanced CCNE1-amplified Solid Tumors

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Phase I: Incidence of dose-limiting toxicities (DLTs)

A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications that occurs within the first 28 days of treatment. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

Time frame: 2 years

Phase I: Incidence of adverse events (AEs) and serious adverse events (SAEs)

Number of participants with AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.

Time frame: 2 years

Phase I: Number of participants with dose interruptions, reductions and discontinuations

Assessment of tolerability. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments are permitted in order to allow patients to continue the study treatment.

Time frame: 2 years

Phase II: PFS rate at 6 months per local response evaluation criteria in solid tumors (RECIST) v1.1

Progression Free Survival (PFS) rate at 6 months is defined as the proportion of patients who are alive and progression-free per RECIST v1.1 at 6 months.

Time frame: 6 months

Secondary Outcomes

Phase I and II: Area under the plasma concentration-time curve (AUC) of ECI830 and ribociclib

Pharmacokinetic (PK) parameters calculated based on ECI830 and ribociclib plasma concentrations by using non-compartmental methods.

Time frame: From pre-dose up to 24 hours post-dose in Cycle 1. One cycle=28 days.

Phase I and II: Maximum observed plasma concentration (Cmax) of ECI830 and ribociclib

PK parameters calculated based on ECI830 and ribociclib plasma concentrations by using non-compartmental methods.

Time frame: From pre-dose up to 24 hours post-dose in Cycle 1. One cycle=28 days.

Phase I and II: Best overall response (BOR) per RECIST v1.1

BOR per 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.

Time frame: 2 years

Phase I and II: Overall response rate (ORR) per RECIST v1.1

ORR per RECIST v1.1 is defined as the proportion of patients with a BOR of Complete response (CR) or Partial response (PR) according to RECIST v1.1 as per local review.

Time frame: 2 years

Phase I and II: Disease control rate (DCR) per RECIST v1.1

DCR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or Stable disease (SD) according to RECIST v1.1 as per local review.

Time frame: 2 years

Phase I and II: Clinical benefit rate (CBR) per RECIST v1.1

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 according to RECIST v1.1 as per local review.

Time frame: 2 years

Phase I and II: Progression Free Survival (PFS) per RECIST v1.1

PFS is defined as the time from the date randomization to the date of the first documented progression or death due to any cause.

Time frame: 2 years

Phase II: Duration of Response (DOR) per RECIST v1.1

DOR per RECIST v1.1 is the time between the first documented response (CR or PR) and the date of progression or death due to any cause.

Time frame: 2 years

Phase II: Overall Survival (OS)

OS is defined as the time between the date of randomization to the date of death due to any cause.

Time frame: 2 years

Phase II: Incidence of adverse events (AEs) and serious adverse events (SAEs)

Number of participants with AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.

Time frame: 2 years

Phase II: Number of participants with dose interruptions, reductions and discontinuations

Assessment of tolerability. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments are permitted in order to allow patients to continue the study treatment.

Time frame: 2 years

Study of ECI830 Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

Overview

Conditions

Interventions

Eligibility

Locations (30)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts