A Phase Ib/II Study to Evaluate Multiple Combination Therapies of FWD1802 in Patients With ER+/HER2- BC

Официальное название

An Open-label, Multicenter, Phase Ib/II Clinical Study to Evaluate the Safety and Efficacy of Multiple Combination Therapies With FWD1802 in Subjects With ER-positive/HER2-negative Unresectable Locally Advanced or Metastatic Breast Cancer

Обзор

This is a Study to Evaluate the Efficacy and Safety of Multiple Combination Therapies with FWD1802 in Subjects with ER-positive/HER2-negative Unresectable Locally Advanced or Metastatic Breast Cancer

Вмешательства

• Препарат FWD1802
  orally QD with 28 days each cycle, treatment till disease progression or intolerable toxicity or withdraw for other reasons
• Препарат Palbociclib 125mg
  Dose: 125 mg Route: Orally Frequency: Once daily (QD) Schedule: Administered for 21 consecutive days, followed by a 7-day treatment break (3-weeks-on/1-week-off), constituting a 28-day cycle
• Препарат Ribociclib 200Mg Oral Tablet
  Dose: 600 mg Route: Orally Frequency: Once daily (QD) Schedule: Administered for 21 consecutive days, followed by a 7-day treatment break, constituting a 28-day cycle
• Препарат Abemaciclib 150 MG
  Dose: 150 mg Route: Orally Frequency: BID Schedule: Everyday
• Препарат Everolimus 10 mg
  Dose: 10 mg Route: Orally Frequency: QD Schedule: Everyday

Первичные конечные точки

• Phase Ib- Dose-Limiting Toxicity (DLT). [Срок оценки: Approximately 1.5 years]
• Phase Ib- Maximum Tolerated Dose (MTD). [Срок оценки: Approximately 1.5 years]
• Phase Ib- Recommended Phase II Dose (RP2D). [Срок оценки: Approximately 1.5 years]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Approximately 2 years]
• Severity Grading of Adverse Events [Срок оценки: Approximately 2 years]
• Clinically Significant Abnormalities in 12-Lead ECG Parameters [Срок оценки: Approximately 2 years]
• Vital Sign Abnormalities [Срок оценки: Approximately 2 years]
• Serious Adverse Events (SAEs) Incidence [Срок оценки: Approximately 2 years]
• Phase II- Investigator-assessed Objective Response Rate (ORR) based on RECIST v1.1. [Срок оценки: Approximately 2 years]

Вторичные конечные точки (12)

• Phase Ib- PK Assessment-Tmax [Срок оценки: Approximately 1.5 years]
• Phase Ib- PK Assessment-Cmax [Срок оценки: Approximately 1.5 years]
• Phase Ib- PK Assessment-AUC0-t [Срок оценки: Approximately 1.5 years]
• Phase Ib- PK Assessment-AUC0-inf [Срок оценки: Approximately 1.5 years]
• Phase Ib- PK Assessment-t1/2 [Срок оценки: Approximately 1.5 years]
• Efficacy Assessment-ORR [Срок оценки: Approximately 2 years]
• Efficacy Assessment-CBR [Срок оценки: Approximately 2 years]
• Efficacy Assessment-DOR [Срок оценки: Approximately 2 years]
• Efficacy Assessment-DCR [Срок оценки: Approximately 1.5 years]
• Efficacy Assessment-PFS [Срок оценки: Approximately 2 years]
• Efficacy Assessment-OS [Срок оценки: Approximately 2 years]
• Pharmacokinetic (PK) Parameters:Plasma Concentration at Each Sampling Time Point. [Срок оценки: Approximately 2 years]

Критерии участия

Критерии включения

• Subjects consent to provide blood samples for centralized laboratory testing of ESR1 mutation status and other biomarkers.
• Histologically or cytologically confirmed ER-positive/HER2-negative locally advanced or metastatic breast cancer
• Subjects must meet at least one of the following criteria: postmenopausal or prior bilateral oophorectomy, or postmenopausal or Premenopausal/perimenopausal women must agree to receive and maintain approved luteinizing hormone-releasing hormone (LHRH) agonist therapy during study treatment
• Prior Therapy Requirements:Subjects must meet all of the following criteria:

• Progression during/after, intolerance to, ineligibility for, or refusal of standard therapy
• Endocrine therapy history:

Recurrence during or within 1 year after completing ≥2 years of adjuvant endocrine therapy;OR progression after ≥1 line of endocrine therapy for advanced breast cancer(ABC) with ≥6 months of maintenance therapy (no restriction on the number of prior endocrine therapy lines).

• ≤2 prior lines of chemotherapy for ABC
• No prior SERD (selective estrogen receptor degrader) therapy except fulvestrant
• Everolimus combination arm: Prior CDK4/6 inhibitor therapy requiredf) CDK4/6 inhibitor combination arm:Permitted ≤1 line of prior non-investigational CDK4/6 inhibitor therapy;If only received adjuvant CDK4/6 inhibitor therapy, recurrence must occur >12 months after treatment completion Note: Antibody-drug conjugates (ADCs) are classified as chemotherapy in this study.
• Phase Ib: At least one evaluable lesion per RECIST v1.1, allowed subjects with osteolytic bone lesion(s) confirmed by CT/MRI.Phase II: At least one measurable lesion per RECIST v1.1.

Subject must have sufficient organ and bone marrow functions at screening.

Критерии исключения

• Leptomeningeal metastasis (carcinomatous meningitis)；Spinal cord compression；Symptomatic or clinically unstable central nervous system (CNS) metastases；
• History or any persistent chronic gastrointestinal disorders or other conditions of impaired absorption that may interfere with oral absorption of the investigational drug
• Symptomatic visceral metastases , or clinically symptomatic and unstable effusions;Pleural effusion;Ascites;Pericardial effusion or Pulmonary lymphangitis carcinomatosa. Prior intracavitary infusion therapy should have more than 14 days of stabilization,
• Prior therapy with any selective estrogen receptor degrader (SERD) or similar agents other than fulvestrant
• Inadequate washout period for prior anticancer therapies.
• Type 1 diabetes mellitus; Type 2 diabetes mellitus with poor glycemic control at screening(applies only to the everolimus combination arm).
• Subjects will be excluded if they meet any of the following:

• Interstitial lung disease or drug-induced ILD history, OR evidence of active pneumonitis on chest CT scan within 4 weeks prior to first study treatment.
• Severe pulmonary disease at screening, including but not limited to:Severe asthma;Severe chronic obstructive pulmonary disease (COPD) Idiopathic
• Uncontrolled hypertension despite antihypertensive therapy, defined as:Systolic blood pressure (SBP) >150 mmHg OR Diastolic blood pressure (DBP) >95 mmHg.
• Active cardiac disease or history of cardiac dysfunction

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center, Shanghai — Шанхай

Идентификаторы

NCT: NCT07002177 · FWD1802-002C

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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