Fulvestaciclib Combined With Anti-HER2 and Endocrine Therapy for HR+/HER2+ Advanced Breast Cancer

Conditions

• Breast Cancer
• HER2-positive Breast Cancer
• HR+/HER2+ Breast Cancer
• Hormone Receptor-positive Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Fulvestaciclib — DRUG
  Oral CDK4/6 inhibitor, 200 mg once daily, 21 days on/7 days off per 28-day cycle.
• Trastuzumab — BIOLOGICAL
  Anti-HER2 monoclonal antibody, 8 mg/kg loading dose then 6 mg/kg IV every 21 days.
• Pertuzumab — BIOLOGICAL
  Anti-HER2 monoclonal antibody, 840 mg loading dose then 420 mg IV every 21 days.
• Fulvestrant — DRUG
  Fulvestrant
• Letrozole — DRUG
  Aromatase inhibitor, 2.5 mg orally once daily.
• Anastrozole — DRUG
  Aromatase inhibitor, 1 mg orally once daily.
• Taxane — DRUG
  Induction chemotherapy (paclitaxel, docetaxel, or nab-paclitaxel) plus HP for 4-8 cycles prior to maintenance therapy.

Study Details

This phase II, multicenter, open-label, randomized controlled trial (FACET study) evaluates the efficacy and safety of fulvestaciclib, a novel oral CDK4/6 inhibitor, combined with anti-HER2 dual blockade (trastuzumab and pertuzumab, HP) and endocrine therapy (ET) in hormone receptor-positive (HR+) and HER2-positive advanced breast cancer (ABC). Patients with HR+/HER2+ ABC without prior systemic therapy for advanced disease are randomized in a 1:1:1 ratio into three arms, stratified by visceral metastasis status (yes vs. no) and metastatic type (de novo vs. recurrent). Arm A: After 4-8 cycles of induction chemotherapy (taxane) plus HP, patients receive fulvestaciclib + HP + ET as maintenance therapy. Arm B: After 4-8 cycles of induction chemotherapy (taxane) plus HP, patients receive HP + ET alone (without fulvestaciclib) as maintenance therapy. Arm C (exploratory): Patients receive upfront fulvestaciclib + HP + ET as first-line therapy without induction chemotherapy (chemo-free). For premenopausal/perimenopausal patients, ovarian function suppression (OFS) is added in all arms. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint is investigator-assessed progression-free survival (PFS) comparing Arm A versus Arm B. Secondary endpoints include PFS (Arm A vs. Arm C), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DoR), cumulative incidence of central nervous system (CNS) metastases, safety, and patient-reported outcomes (PROs).

Key Dates

First listed

Jul 21, 2026

Start date

Oct 1, 2026

Status verified

Jul 2026

Primary completion

Aug 31, 2030

Completion

Dec 31, 2032

Study Design

Enrollment

240 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Fulvestaciclib + HP + ET Maintenance
  After 4-8 cycles of induction chemotherapy (taxane) plus trastuzumab and pertuzumab (HP), participants receive maintenance therapy with oral fulvestaciclib 200 mg daily (21 days on, 7 days off, 28-day cycle), HP (trastuzumab 8 mg/kg loading then 6 mg/kg IV Q3W; pertuzumab 840 mg loading then 420 mg IV Q3W), and endocrine therapy (ET: fulvestrant 500 mg IM on Days 1,15,29 then monthly, or letrozole 2.5 mg or anastrozole 1 mg PO daily). Premenopausal/perimenopausal patients also receive ovarian function suppression (OFS). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or death.
• Active Comparator: HP + ET Maintenance (Control)
  After 4-8 cycles of induction chemotherapy (taxane) plus trastuzumab and pertuzumab (HP), participants receive maintenance therapy with HP (trastuzumab 8 mg/kg loading then 6 mg/kg IV Q3W; pertuzumab 840 mg loading then 420 mg IV Q3W) and endocrine therapy (ET: fulvestrant 500 mg IM on Days 1,15,29 then monthly, or letrozole 2.5 mg or anastrozole 1 mg PO daily) without fulvestaciclib. Premenopausal/perimenopausal patients also receive ovarian function suppression (OFS). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or death.
• Experimental: Upfront Fulvestaciclib + HP + ET (Chemo-free)
  Participants receive first-line therapy with oral fulvestaciclib 200 mg daily (21 days on, 7 days off, 28-day cycle), HP (trastuzumab 8 mg/kg loading then 6 mg/kg IV Q3W; pertuzumab 840 mg loading then 420 mg IV Q3W), and endocrine therapy (ET: fulvestrant 500 mg IM on Days 1,15,29 then monthly, or letrozole 2.5 mg or anastrozole 1 mg PO daily) without induction chemotherapy. Premenopausal/perimenopausal patients also receive ovarian function suppression (OFS). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Primary Outcome Measure

Progression-Free Survival (PFS) Assessed by Investigator [ Time Frame: From randomization to first documented progression per RECIST 1.1 or death, assessed every 6 weeks for 12 weeks then every 12 weeks until progression, up to 6 years. ]

Central Contacts

• Jian Zhang, MD
  +86 18017312991
  [email protected]

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