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

Phase 1

Not yet recruiting

• Conditions: Metastatic Breast Cancer; Breast Cancer Stage I; Breast Cancer Stage II; Locally Advanced Breast Cancer (LABC); ER+ Breast Cancer
• Interventions: Drug: FWD1802; Drug: Palbociclib 125mg; Drug: Ribociclib 200Mg Oral Tablet; Drug: Abemaciclib 150 MG; Drug: Everolimus 10 mg

• Registration Number: NCT07002177
• Lead Sponsor: Forward Pharmaceuticals Co., Ltd.

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-14
• Study First Submitted QC: 2025-05-24
• Last Update Submitted: 2025-05-24
• Study Start: 2025-06-01
• Study First Posted: 2025-06-03
• Last Update Posted: 2025-06-03
• Primary Completion: 2028-05-01
• Study Completion: 2028-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 196

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FWD1802 in combination with Palbociclib (CDK4/6 inhibitor) with or without LHRH agonist；	FWD1802	-
FWD1802 in combination with Palbociclib (CDK4/6 inhibitor) with or without LHRH agonist；	Palbociclib 125mg	-
FWD1802 in combination with Ribociclib (CDK4/6 inhibitor) with or without LHRH agonist	FWD1802	-
FWD1802 in combination with Ribociclib (CDK4/6 inhibitor) with or without LHRH agonist	Ribociclib 200Mg Oral Tablet	-
FWD1802 in combination with Abemaciclib (CDK4/6 inhibitor) with or without LHRH agonist	FWD1802	-
FWD1802 in combination with Abemaciclib (CDK4/6 inhibitor) with or without LHRH agonist	Abemaciclib 150 MG	-
FWD1802 in combination with Everolimus (mTOR inhibitor) with or without LHRH agonist	FWD1802	-
FWD1802 in combination with Everolimus (mTOR inhibitor) with or without LHRH agonist	Everolimus 10 mg	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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）
Efficacy Assessment-DCR	Approximately 1.5 years	Disease control rate (DCR)
Phase Ib- PK Assessment-Tmax	Approximately 1.5 years	Time to Cmax (Tmax).
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-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.
Pharmacokinetic (PK) Parameters:Plasma Concentration at Each Sampling Time Point.	Approximately 2 years