A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer

Официальное название

A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination With Giredestrant in Comparison With Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor

Обзор

The purpose of this study is to assess the safety of GDC-4198 alone and in combination with giredestrant and also the efficacy of GDC-4198 + giredestrant versus abemaciclib + giredestrant in participants with locally advanced or metastatic ER+, HER2- breast cancer. The study consists of 2 phases: Phase Ib and Phase II. Phase Ib will evaluate the safety and pharmacokinetics (PK) of GDC-4198 alone and in combination with giredestrant. Phase II stage will compare the activity and safety of GDC-4198 and giredestrant with abemaciclib and giredestrant.

Вмешательства

• Препарат GDC-4198
  GDC-4198 will be administered orally.
• Препарат Giredestrant
  Giredestrant will be administered orally.
• Препарат Abemaciclib
  Abemaciclib will be administered orally.

Первичные конечные точки

• Phase Ib: Incidence and Severity of Adverse Events (AEs) [Срок оценки: Up to 36 months]
• Phase Ib: Number of Participants With Dose-Limiting Toxicity (DLTs) [Срок оценки: From Day 1 to Day 28 of Cycle 1 (1 cycle=28 days)]
• Phase II: Progression-free Survival (PFS) [Срок оценки: Up to 36 months]

Вторичные конечные точки (11)

• Phase Ib: Objective Response Rate (ORR) [Срок оценки: Up to 36 months]
• Phase Ib: Clinical Benefit Rate (CBR) [Срок оценки: Up to 36 months]
• Phase II: ORR [Срок оценки: Up to 36 months]
• Phase II: Duration of Response (DOR) [Срок оценки: Up to 36 months]
• Phase II: CBR [Срок оценки: Up to 36 months]
• Phase II: Overall Survival (OS) [Срок оценки: Up to 36 months]
• Phase II: OS Rate at 6 Months and 12 Months [Срок оценки: Month 6, Month 12]
• Phase II: PFS Rate at 6 Months and 12 Months [Срок оценки: Month 6, Month 12]
• Phase II: Incidence and Severity of Adverse Events (AEs) [Срок оценки: Up to 36 months]
• Phase II: Plasma Concentration of GDC-4198 [Срок оценки: Up to 36 months]
• Phase II: Recommended Dose of GDC-4198 [Срок оценки: Up to 36 months]

Критерии участия

Критерии включения

• Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic.
• Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines.
• Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and approved endocrine therapy (ET) in the locally advanced or metastatic setting.
• Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy >= 6 months.

Критерии исключения

• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines.
• Have received more than one-line of therapy for locally advanced or metastatic disease.
• Have received prior chemotherapy for metastatic breast cancer.
• Treatment with an approved oral ET within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug.
• Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption
• History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.
• Known allergy or hypersensitivity to any component of the study treatments.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 20 центров

• City of Hope — Duarte
• City of Hope - Orange County Lennar Foundation Cancer Center — Irvine
• UC San Diego Moores Cancer Center — La Jolla
• UCSF Helen Diller Family CCC — San Francisco
• Sylvester Comprehensive Cancer Center — Miami
• Moffitt Cancer Center — Tampa
• Winship Cancer Institute of Emory University — Atlanta
• City of Hope® Cancer Center Chicago — Zion
• … и ещё 12 центров

South Korea · 6 центров

• Gangnam Severance Hospital, Yonsei University Health System — Seoul
• Seoul National University Bundang Hospital — Seongnam-si
• Seoul National University Hospital — Seoul
• Asan Medical Center. — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul

Бразилия · 5 центров

• Hospital do Cancer de Pernambuco - HCP — Recife
• ONCOSITE Centro de Pesquisa Clínica Em Oncologia — Ijuí
• Irmandade Da Santa Casa de Misericordia de Porto Alegre — Porto Alegre
• Hospital de Clinicas de Porto Alegre (HCPA) - PPDS — Porto Alegre
• Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira - ICESP — São Paulo

Франция · 5 центров

• Institut Jean Godinot — Reims
• Gustave Roussy — Villejuif
• Centre Francois Baclesse — Caen
• Centre Oscar Lambret — Lille
• Centre Eugene Marquis — Rennes

Испания · 5 центров

• Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON — Barcelona
• Hospital Beata Maria Ana — Madrid
• Hospital General Universitario Gregorio Maranon — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Clinico Universitario de Valencia — Valencia

Италия · 4 центра

• IRCCS Azienda Ospedaliero Universitaria di Bologna — Bologna
• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS — Meldola
• ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia — Brescia
• Ospedale San Raffaele S.r.l. - PPDS — Milan

Австралия · 2 центра

• St Vincent's Hospital Sydney — Darlinghurst
• Cancer Research SA — Adelaide

Китай · 2 центра

• Shandong Cancer Hospital — Цзинань
• Fudan University Shanghai Cancer Center - Pudong Campus — Шанхай

Германия · 2 центра

• KEM - Evang. Huyssens-Stiftung Essen-Huttrop — Essen
• Universitatsklinikum Hamburg-Eppendorf — Hamburg

Канада · 1 центр

• Princess Margaret Hospital — Toronto

Идентификаторы

NCT: NCT07100106 · GO46021 · 2025-521128-31-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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