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

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.

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 or extensive-stage small cell lung cancer (ES-SCLC), 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.

Interventions

• Drug ECI830
  Experimental
• Drug ribociclib
  Approved medication
• Drug fulvestrant
  Approved medication

Primary outcome measures

• Phase I: Incidence of dose-limiting toxicities (DLTs) [Time frame: 2 years]
• Phase I: Incidence of adverse events (AEs) and serious adverse events (SAEs) [Time frame: 2 years]
• Phase I: Number of participants with dose interruptions, reductions and discontinuations [Time frame: 2 years]
• Phase II: PFS rate at 6 months per local response evaluation criteria in solid tumors (RECIST) v1.1 [Time frame: 6 months]

Secondary outcome measures (11)

• Phase I and II: Area under the plasma concentration-time curve (AUC) of ECI830 and ribociclib [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 [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 [Time frame: 2 years]
• Phase I and II: Overall response rate (ORR) per RECIST v1.1 [Time frame: 2 years]
• Phase I and II: Disease control rate (DCR) per RECIST v1.1 [Time frame: 2 years]
• Phase I and II: Clinical benefit rate (CBR) per RECIST v1.1 [Time frame: 2 years]
• Phase I and II: Progression Free Survival (PFS) per RECIST v1.1 [Time frame: 2 years]
• Phase II: Duration of Response (DOR) per RECIST v1.1 [Time frame: 2 years]
• Phase II: Overall Survival (OS) [Time frame: 2 years]
• Phase II: Incidence of adverse events (AEs) and serious adverse events (SAEs) [Time frame: 2 years]
• Phase II: Number of participants with dose interruptions, reductions and discontinuations [Time frame: 2 years]

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.

Patients with ES-SCLC and disease progression on or after standard of care (SoC). For dose expansion only: no more than 2 prior lines of therapy for advanced or metastatic disease are allowed.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• University of California LA — Los Angeles
• Florida Cancer Specialists — Fort Myers
• Dana Farber Cancer Institute — Boston
• WA Uni School Of Med — St Louis
• Memorial Sloan Kettering — New York
• SCRI Oncology Partners — Nashville
• MD Anderson Cancer Center Uni of Te — Houston
• Fred Hutch Cancer Research — Seattle

Germany · 3 centers

• Novartis Investigative Site — Freiburg im Breisgau
• Novartis Investigative Site — Heidelberg
• Novartis Investigative Site — Ulm

Australia · 2 centers

• Novartis Investigative Site — Clayton
• Novartis Investigative Site — Melbourne

Canada · 2 centers

• Novartis Investigative Site — Toronto
• Novartis Investigative Site — Montreal

China · 2 centers

• Novartis Investigative Site — Nanjing
• Novartis Investigative Site — Xian

Denmark · 2 centers

• Novartis Investigative Site — Copenhagen
• Novartis Investigative Site — Odense C

France · 2 centers

• Novartis Investigative Site — Bordeaux
• Novartis Investigative Site — Saint-Herblain

Israel · 2 centers

• Novartis Investigative Site — Haifa
• Novartis Investigative Site — Tel Aviv

Italy · 2 centers

• Novartis Investigative Site — Modena
• Novartis Investigative Site — Milan

Spain · 2 centers

• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Barcelona

Czechia · 1 center

• Novartis Investigative Site — Brno

Japan · 1 center

• Novartis Investigative Site — Chuo Ku

Singapore · 1 center

• Novartis Investigative Site — Singapore

South Korea · 1 center

• Novartis Investigative Site — Seoul

Taiwan · 1 center

• Novartis Investigative Site — Tainan

United Kingdom · 1 center

• Novartis Investigative Site — London

Identifiers

NCT: NCT06726148 · CECI830A12101 · 2024-517281-42

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗