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

NCT07002177 | Recruiting Phase 1

• 1 other identifier: FWD1802-002C
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

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

Conditions

Metastatic Breast Cancer; Breast Cancer Stage I; Breast Cancer Stage II; Locally Advanced Breast Cancer (LABC); ER+ Breast Cancer

Outcome Measures

Primary Outcomes (9)

• 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)

  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).

  Approximately 2 years

• Severity Grading of Adverse Events

  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).

  Approximately 2 years

• Clinically Significant Abnormalities in 12-Lead ECG Parameters

  Number of participants with clinically significant changes in electrocardiogram parameters from baseline. Assessed parameters: QTc interval, PR interval, QRS duration, heart rate.

  Approximately 2 years

• Vital Sign Abnormalities

  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).

  Approximately 2 years

• 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 Outcomes (12)

• Phase Ib- PK Assessment-Tmax

  Approximately 1.5 years

• Phase Ib- PK Assessment-Cmax

  Approximately 1.5 years

• Phase Ib- PK Assessment-AUC0-t

  Approximately 1.5 years

• Phase Ib- PK Assessment-AUC0-inf

  Approximately 1.5 years

• Phase Ib- PK Assessment-t1/2

  Approximately 1.5 years

Study Arms (4)

FWD1802 in combination with Palbociclib (CDK4/6 inhibitor) with or without LHRH agonist；

EXPERIMENTAL

Drug: FWD1802; Drug: Palbociclib 125mg

FWD1802 in combination with Ribociclib (CDK4/6 inhibitor) with or without LHRH agonist

EXPERIMENTAL

Drug: FWD1802; Drug: Ribociclib 200Mg Oral Tablet

FWD1802 in combination with Abemaciclib (CDK4/6 inhibitor) with or without LHRH agonist

EXPERIMENTAL

Drug: FWD1802; Drug: Abemaciclib 150 MG

FWD1802 in combination with Everolimus (mTOR inhibitor) with or without LHRH agonist

EXPERIMENTAL

Drug: FWD1802; Drug: Everolimus 10 mg

Interventions

FWD1802 DRUG

orally QD with 28 days each cycle, treatment till disease progression or intolerable toxicity or withdraw for other reasons

FWD1802 in combination with Abemaciclib (CDK4/6 inhibitor) with or without LHRH agonist; FWD1802 in combination with Everolimus (mTOR inhibitor) with or without LHRH agonist; FWD1802 in combination with Palbociclib (CDK4/6 inhibitor) with or without LHRH agonist；; FWD1802 in combination with Ribociclib (CDK4/6 inhibitor) with or without LHRH agonist

Palbociclib 125mg DRUG

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

FWD1802 in combination with Palbociclib (CDK4/6 inhibitor) with or without LHRH agonist；

Ribociclib 200Mg Oral Tablet DRUG

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

FWD1802 in combination with Ribociclib (CDK4/6 inhibitor) with or without LHRH agonist

Abemaciclib 150 MG DRUG

Dose: 150 mg Route: Orally Frequency: BID Schedule: Everyday

FWD1802 in combination with Abemaciclib (CDK4/6 inhibitor) with or without LHRH agonist

Everolimus 10 mg DRUG

Dose: 10 mg Route: Orally Frequency: QD Schedule: Everyday

FWD1802 in combination with Everolimus (mTOR inhibitor) with or without LHRH agonist

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Forward Pharmaceuticals Co., Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center, Shanghai

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; ribociclib; Tablets; abemaciclib; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Sirolimus; Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Jinglin Xu

CONTACT

18964533182; xujl@forward-pharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: June 3, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

CN (1)