Mecapegfilgrastim for the Prevention of Dalpiciclib -Induced Neutropenia in Advanced Breast Cancer

Study Overview
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Brief Summary
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Neutropenia is a common complication from dalpiciclib. Mecapegfilgramtim (code name HHPG-19K), a long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF), has been developed. The study aim to evaluate the safety and efficiency of mecapegfilgrastim for prophylaxis of dalpiciclib -induced neutropenia in patients with advanced HR+/HER2- breast cancer.

Official Title
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Efficacy and Safety of Mecapegfilgrastim for Prophylaxis of Dalpiciclib -Induced Neutropenia in Patients With Advanced HR+/HER2- Breast Cancer: a Open-label, Multicenter, Investigator-initiated, Randomized Controlled Phase II Trial

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Mecapegfilgrastim
* Drug: dalpiciclib
* Drug: exemestane, fulvestrant, letrozole, tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18. Pathologically confirmed advanced HR+/HER2- breast cancer: there is evidence of focal recurrence or metastasis, which is not suitable for surgical resection or radiotherapy for the purpose of cure. No more than one line of chemotherapy is allowed for patients with recurrent and metastatic diseases. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Measurable lesions meeting RECIST 1.1 criteria or only bone metastases. For patients with brain metastases, there is need for local treatment, and the brain lesions are stable for ≥ 3 months, and no need for dexamethasone or mannitol. Adequate organ function: (I) adequate hematologic function: hemoglobin ≥90 g/L, absolute neutrophil count (ANC) ≥2.0×109/L, platelet count (PLT) ≥100×109/L; (II) adequate renal and hepatic function. Negative pregnancy test. Exclusion Criteria: Previous pathological diagnosis of HER2 positive breast cancer. Relapse and metastasis occurred after receiving neoadjuvant endocrine therapy or adjuvant therapy for 2 years, or disease progression or recurrence occurred within 12 months or 12 months after completion of adjuvant endocrine therapy. Previous treatment with cdk4/6 inhibitors. Major surgery, chemotherapy, radiotherapy, any research drug or other anti-cancer treatment within 2 weeks before entering the trial. Any other malignant tumor diagnosed within 3 years before entering the study, except non-melanoma skin cancer, basal cell or squamous cell skin cancer or cervical carcinoma in situ after radical treatment. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 1000 IU/ml), hepatitis C (HCV antibody positive and HCV-RNA higher than the detection limit of the analytical method) or combined hepatitis B and hepatitis C co-infection. Within 6 months before entering the study, the following conditions occurred: myocardial infarction, severe / unstable angina pectoris, NYHA grade 2 or above cardiac insufficiency, persistent arrhythmia ≥ grade 2 (according to nci-ctcae version 5.0), atrial fibrillation at any level, coronary / peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism). Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mecapegfilgrastim +dalpiciclib + endocrine therapy<br>Mecapegfilgrastim / dalpiciclib / Endocrine therapy (exemestane, fulvestrant, letrozole, tamoxifen) | Drug: Mecapegfilgrastim<br>* Mecapegfilgrastim<br>Drug: dalpiciclib<br>* dalpiciclib<br>Drug: exemestane, fulvestrant, letrozole, tamoxifen<br>* endocrine therapy<br>|
| Active Comparator: dalpiciclib + endocrine therapy<br>dalpiciclib / Endocrine therapy (exemestane, fulvestrant, letrozole, tamoxifen) | Drug: dalpiciclib<br>* dalpiciclib<br>Drug: exemestane, fulvestrant, letrozole, tamoxifen<br>* endocrine therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of grade ≥3 neutropenia at the end of cycle 2 (each cycle is 28 days) | The incidence of grade ≥3 neutropenia in cycle 2: defined as ANC <1.0×109/L at the end of Cycle 1 (each cycle is 28 days). | at the end of cycle 2 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of grade ≥3 neutropenia at the end of all cycles (each cycle is 28 days) | The incidence of grade ≥3 neutropenia in cycle 2: defined as ANC <1.0×109/L at the end of All Cycles (each cycle is 28 days). | through study completion, an average of 2 years | 
| Breast-Q scores | Breast-Q scores for patient's quality of life | through study completion, an average of 2 years | 
| Progression-free Survival | Progression-free Survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 
| Overall Survival | Overall Survival | From date of randomization until the date of death from any cause, assessed up to 60 months | 
| Relative dose intensity of dalpiciclib | Relative dose intensity of dalpiciclib | through study completion, an average of 2 years |