Clinical trial NCT07002177: A Phase Ib/II Study to Evaluate Multiple Combination Therapies of FWD1802 in Patients With ER+/HER2- BC
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Breast Cancer Stage I
Breast Cancer Stage II
Locally Advanced Breast Cancer (LABC)
ER+ Breast Cancer
Lead sponsor: Forward Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-06-03
Enrollment: 196
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Phase Ib- Dose-Limiting Toxicity (DLT).
timeFrame: Approximately 1.5 years
measure: Phase Ib- Maximum Tolerated Dose (MTD).
timeFrame: Approximately 1.5 years
measure: Phase Ib- Recommended Phase II Dose (RP2D).
timeFrame: Approximately 1.5 years
measure: Incidence of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Approximately 2 years
measure: Severity Grading of Adverse Events
timeFrame: Approximately 2 years
measure: Clinically Significant Abnormalities in 12-Lead ECG Parameters
timeFrame: Approximately 2 years
measure: Vital Sign Abnormalities
timeFrame: Approximately 2 years
measure: Serious Adverse Events (SAEs) Incidence
timeFrame: Approximately 2 years
measure: Phase II- Investigator-assessed Objective Response Rate (ORR) based on RECIST v1.1.
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Phase Ib- PK Assessment-Tmax
timeFrame: Approximately 1.5 years
measure: Phase Ib- PK Assessment-Cmax
timeFrame: Approximately 1.5 years
measure: Phase Ib- PK Assessment-AUC0-t
timeFrame: Approximately 1.5 years
measure: Phase Ib- PK Assessment-AUC0-inf
timeFrame: Approximately 1.5 years
measure: Phase Ib- PK Assessment-t1/2
timeFrame: Approximately 1.5 years
measure: Efficacy Assessment-ORR
timeFrame: Approximately 2 years
measure: Efficacy Assessment-CBR
timeFrame: Approximately 2 years
measure: Efficacy Assessment-DOR
timeFrame: Approximately 2 years
measure: Efficacy Assessment-DCR
timeFrame: Approximately 1.5 years
measure: Efficacy Assessment-PFS
timeFrame: Approximately 2 years
measure: Efficacy Assessment-OS
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK) Parameters:Plasma Concentration at Each Sampling Time Point.
timeFrame: Approximately 2 years
Other outcomes:
Locations:
Study officials:
References: