Breast Cancer Stage I, Breast Cancer Stage II, ER+ Breast Cancer, Locally Advanced Breast Cancer (LABC), Metastatic Breast Cancer
Conditions
Brief summary
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
Interventions
DRUGFWD1802
orally QD with 28 days each cycle, treatment till disease progression or intolerable toxicity or withdraw for other reasons
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
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
Dose: 150 mg Route: Orally Frequency: BID Schedule: Everyday
DRUGEverolimus 10 mg
Dose: 10 mg Route: Orally Frequency: QD Schedule: Everyday
Sponsors
Forward Pharmaceuticals Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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: 1. Progression during/after, intolerance to, ineligibility for, or refusal of standard therapy 2. 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). 3. ≤2 prior lines of chemotherapy for ABC 4. No prior SERD (selective estrogen receptor degrader) therapy except fulvestrant 5. 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.
Exclusion criteria
* 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: 1. 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. 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib- Dose-Limiting Toxicity (DLT). | Approximately 1.5 years | — |
| Phase Ib- Maximum Tolerated Dose (MTD). | Approximately 1.5 years | — |
| Phase Ib- Recommended Phase II Dose (RP2D). | Approximately 1.5 years | — |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Approximately 2 years | Number and proportion of participants experiencing any treatment-emergent adverse event during the study period. Assessment criteria: Events will be categorized as related or unrelated to study drug based on investigator's causality assessment. Reporting format: Frequency counts and percentages stratified by severity grade (Grade 1-5 as per NCI-CTCAE v5.0). |
| Severity Grading of Adverse Events | Approximately 2 years | Maximum severity grade of treatment-emergent adverse events experienced by participants. Assessment tool: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Reporting format: Proportion of participants with events in each severity category (Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=death). |
| Clinically Significant Abnormalities in 12-Lead ECG Parameters | Approximately 2 years | Number of participants with clinically significant changes in electrocardiogram parameters from baseline. Assessed parameters: QTc interval, PR interval, QRS duration, heart rate. |
| Vital Sign Abnormalities | Approximately 2 years | Proportion of participants with clinically significant deviations in vital signs: Parameters: Systolic/diastolic blood pressure (mmHg), heart rate (bpm), respiratory rate (breaths/min), body temperature (°C). |
| Serious Adverse Events (SAEs) Incidence | Approximately 2 years | — |
| Phase II- Investigator-assessed Objective Response Rate (ORR) based on RECIST v1.1. | Approximately 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Assessment-PFS | Approximately 2 years | Progression-free survival (PFS) by IRC according to RECIST 1.1.PFS is defined as time from the first dose until disease progression or death from any cause, whichever occurs first. |
| Efficacy Assessment-DCR | Approximately 1.5 years | Disease control rate (DCR) |
| Pharmacokinetic (PK) Parameters:Plasma Concentration at Each Sampling Time Point. | Approximately 2 years | — |
| Efficacy Assessment-OS | Approximately 2 years | Overall survival (OS).OS is defined as time from date of the first dose to date of death due to any cause. |
| Phase Ib- PK Assessment-Tmax | Approximately 1.5 years | Time to Cmax (Tmax). |
| Phase Ib- PK Assessment-Cmax | Approximately 1.5 years | Maximum plasma concentration (Cmax) |
| Phase Ib- PK Assessment-AUC0-t | Approximately 1.5 years | Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC0-t) |
| Phase Ib- PK Assessment-AUC0-inf | Approximately 1.5 years | The area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) |
| Phase Ib- PK Assessment-t1/2 | Approximately 1.5 years | elimination half-life time (t1/2) |
| Efficacy Assessment-ORR | Approximately 2 years | Tumor response assessments by the corresponding criteria by RECIST v1.1 to assess Objective response rate (ORR) |
| Efficacy Assessment-CBR | Approximately 2 years | Clinical benefit rate (CBR) |
| Efficacy Assessment-DOR | Approximately 2 years | Duration of response (DoR） |
Countries
China
Contacts
Primary ContactJinglin Xu
Outcome results
None listed