Combining FWD1802 with CDK4/6 inhibitors or everolimus for ER+/HER2- advanced breast cancer

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

This trial tests whether adding FWD1802 to CDK4/6 inhibitors or everolimus helps people with ER-positive/HER2-negative unresectable locally advanced or metastatic breast cancer who have progressed on or cannot use standard therapy.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 196 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Forward Pharmaceuticals Co., Ltd. (industry)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT07002177 on ClinicalTrials.gov

What this trial studies

This Phase Ib/II interventional study explores multiple combination regimens pairing the investigational agent FWD1802 with approved targeted therapies (palbociclib, ribociclib, abemaciclib, or everolimus) in patients with ER+/HER2- locally advanced or metastatic breast cancer. Dose-finding and safety lead the early phase portions, with expansion cohorts to measure anti-tumor activity and biomarkers. Participants must provide blood for centralized ESR1 mutation and other biomarker testing and meet prior-therapy criteria related to endocrine treatment. The study is single-site listed at Fudan University Shanghai Cancer Center and enrolls patients who can comply with the protocol and required sample collection.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed ER-positive/HER2-negative unresectable locally advanced or metastatic breast cancer who progressed on or were intolerant of standard therapies and agree to biomarker blood sampling and, if applicable, LHRH agonist therapy.

Not a fit: Patients with HER2-positive disease, early-stage resectable breast cancer, or those unable to tolerate CDK4/6 inhibitors, everolimus, or required blood sampling/hormone suppression are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, the combinations could extend disease control or overcome endocrine resistance in patients with ER+/HER2- advanced breast cancer.

How similar studies have performed: Combining CDK4/6 inhibitors with endocrine therapy has improved outcomes in ER+ metastatic breast cancer, but adding novel agents like FWD1802 remains experimental and less tested.

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

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center, Shanghai — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Jinglin Xu

Conditions: Metastatic Breast Cancer, Breast Cancer Stage I, Breast Cancer Stage II, Locally Advanced Breast Cancer, ER+ Breast Cancer