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

Forward Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: Ribociclib 200Mg Oral Tablet; Drug: Abemaciclib 150 MG; Drug: Palbociclib 125mg; Drug: Everolimus 10 mg; Drug: FWD1802

Study type: Interventional

Funder types: Industry

Identifiers

NCT07002177

FWD1802-002C

Details and patient eligibility

About

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

Enrollment: 196 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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196 participants in 4 patient groups

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

Experimental group

Treatment:

Drug: FWD1802

Drug: Palbociclib 125mg

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

Experimental group

Treatment:

Drug: FWD1802

Drug: Ribociclib 200Mg Oral Tablet

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

Experimental group

Treatment:

Drug: FWD1802

Drug: Abemaciclib 150 MG

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

Experimental group

Treatment:

Drug: Everolimus 10 mg

Drug: FWD1802