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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат ECI830
  Experimental
• Препарат ribociclib
  Approved medication
• Препарат fulvestrant
  Approved medication

Первичные конечные точки

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

Вторичные конечные точки (11)

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

Критерии участия

Критерии включения

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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• 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

Германия · 3 центра

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

Австралия · 2 центра

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

Канада · 2 центра

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

Китай · 2 центра

• Novartis Investigative Site — Нанкин
• Novartis Investigative Site — Сиань

Дания · 2 центра

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

Франция · 2 центра

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

Израиль · 2 центра

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

Италия · 2 центра

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

Испания · 2 центра

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

Чехия · 1 центр

• Novartis Investigative Site — Brno

Япония · 1 центр

• Novartis Investigative Site — Chuo Ku

Сингапур · 1 центр

• Novartis Investigative Site — Singapore

South Korea · 1 центр

• Novartis Investigative Site — Seoul

Тайвань · 1 центр

• Novartis Investigative Site — Tainan

Великобритания · 1 центр

• Novartis Investigative Site — London

Идентификаторы

NCT: NCT06726148 · CECI830A12101 · 2024-517281-42

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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