Advanced/Metastatic Breast Cancer, HER2-Positive Metastatic Breast Cancer
Conditions
Keywords
Dalpiciclib, Dalpiciclib Plus Anti-HER2 Therapy and Endocrine Therapy
Brief summary
Efficacy and Safety of Dalpiciclib Combined with Anti-HER2 Targeted Therapy and Endocrine Therapy as First-line Maintenance Treatment for Patients with Recurrent or Metastatic Hormone-Receptor-Positive, HER2-positive Breast Cancer.
Detailed description
This is a multicenter, single-arm, open-label, phase II clinical trial evaluating the efficacy and safety of dalpiciclib (a novel oral CDK4/6 inhibitor) combined with anti-HER2 therapy and endocrine therapy as maintenance treatment in patients with hormone receptor-positive (HR+)/HER2-positive metastatic breast cancer who have completed induction systemic therapy without disease progression. Triple-positive (HR+/HER2+) metastatic breast cancer represents a unique subtype requiring dual pathway inhibition. Current standard first-line induction therapy includes taxane-based chemotherapy combined with trastuzumab and pertuzumab (THP) or pyrotinib (THPy), followed by maintenance with anti-HER2 therapy plus endocrine therapy. However, approximately 50% of patients progress within 18 months during maintenance therapy. This study explores the addition of dalpiciclib to standard anti-HER2 and endocrine maintenance therapy to prolong progression-free survival. Dalpiciclib, the first domestically developed CDK4/6 inhibitor in China, has demonstrated favorable efficacy and a manageable safety profile in HR+/HER2- advanced breast cancer, with a lower incidence of febrile neutropenia and no observed interstitial lung disease.
Interventions
DRUGDalpiciclib
Oral CDK4/6 inhibitor (dose modification permitted for toxicity management)
Subcutaneous, 600mg Q3W; IV: 8mg/kg (loading) → 6mg/kg Q3W
DRUGPertuzumab
IV: 840mg (loading) → 420mg Q3W
DRUGPyrotinib
240mg qd Week 1 → 320mg qd from Week 2 (max dose); loperamide prophylaxis for diarrhea
Letrozole 2.5mg, Anastrozole 1mg, Exemestane 25mg, or Fulvestrant 0.5g IM on Days 1, 28 (initial: Days 1, 15, 28)
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Females aged 18 to 75 years with pathologically confirmed metastatic or locally advanced unresectable breast cancer. 2. Hormone receptor (HR)-positive and HER2-positive. 3. Patients with no evidence of disease progression (including CR, PR, or SD)after 4-8 cycles of first-line systemic anti-tumor therapy. 4. ECOG Performance Status: 0-1.
Exclusion criteria
1. Symptomatic active brain metastases or extensive leptomeningeal metastases. 2. History of Grade 3 or 4 allergic reaction related to the study drugs. 3. Currently receiving other anti-tumor therapies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the last participant completes treatment. | Time from enrollment to radiographic disease progression (per RECIST 1.1) or death from any cause, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the last participant completes treatment. | Proportion of patients achieving Complete Response (CR) or Partial Response (PR) per RECIST 1.1 |
| Overall Survival (OS) | From randomization until the end of the study (approximately 36 months) | Time from enrollment to death from any cause |
| Safety and Tolerability | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the last participant completes treatment. | Incidence, type, severity, and relationship of adverse events (AEs) graded by NCI CTCAE v5.0 |
| Disease-Specific Quality of Life Assessed by EORTC QLQ-BR45 | From the date of enrollment until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 2 years after the last participant completes treatment. | Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer-Specific Module (EORTC QLQ-BR45). The EORTC QLQ-BR45 contains 45 items divided into functional and symptom scales evaluating breast cancer-specific issues and treatment side effects. All scales range in score from 0 to 100. A higher score for a functional scale represents a higher/healthy level of functioning, whereas a higher score for a symptom scale represents a higher level of breast cancer-related symptomatology or treatment-related problems. |
| Quality of Life Assessed by EORTC QLQ-C30 | From the date of enrollment until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 2 years after the last participant completes treatment. | Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 consists of 30 items incorporating 5 functional scales, 3 symptom scales, a global health status scale, and 6 single items. All scales and single-item measures range in score from 0 to 100. A higher score for a functional scale or global health status represents a higher/healthy level of functioning, whereas a higher score for a symptom scale/item represents a higher level of symptomatology or problems. |
Countries
China
Contacts
CONTACTChen Doctor Chen, PhD / Doctorate
Outcome results
None listed