TQB3616 Capsules Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Previously Treated Breast Cancer in Clinical Trail

Study Overview
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Brief Summary
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This is a Phase III, a randomized, double-blind, parallel , multi-center trail to evaluate the efficacy and safety of TQB3616 capsules plus fulvestrant compared to placebo plus fulvestrant in participants with estrogen receptor-positive, HER2-Negative Advanced Breast Cancer. Approximately 287 women will be randomized to either TQB3616 plus fulvestrant or TQB3616-matching placebo plus fulvestrant. Randomization will follow a 2:1 randomization ratio,the experimental is 191; the Placebo Comparator is 96.

Official Title
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A Phase III,Randomized, Double-blind, Paralle, Multi-center Study to Evaluate the Efficacy and Safety of TQB3616 Capsules Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Participants With Hormone Receptor (HR)-Positive, Human Epidermal Growth Factor Receptor(EGFR) 2-Negative Advanced Breast Cancer

Conditions
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HR-positive,HER2-negative in Advanced Breast Cancer

Intervention / Treatment
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* Drug: TQB3616 capsules
* Drug: TQB3616-matching placebo
* Drug: Fluvestrin injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 The subjects voluntarily joined the study and signed the informed consent, with good compliance. 2 Age: 18-75 years old (upon signing the informed consent);ECOG PS score: 0 1; Expected survival ≥3 months. 3 participants with estrogen receptor-positive, HER2-Negative Advanced Breast Cancer were identified by pathological testing. 4 Patients at the relapse/metastatic stage were allowed to receive no more than 1 line of rescue chemotherapy or rescue endocrine therapy. 5 Confirmation of at least one measurable lesion according to RECIST1.1 criteria. 6 The main organs are functioning well and meet the following criteria: Routine blood examination criteria (no blood transfusion or hematopoietic stimulus drug correction within 7 days before screening) : a) hemoglobin (Hb) ≥100g/L; b) neutrophils absolute value (NEUT) ≥1.5×10^9/L; c) Platelet count (PLT) ≥90×10^9/L. Biochemical tests should meet the following criteria: a) Total bilirubin (TBIL) ≤2.5 times the upper limit of normal (ULN); b) Alanine transferase (ALT) and aspartate transferase (AST) ≤2.5×ULN.ALT and AST≤5×ULN with liver metastasis. c) Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance rate (CCR) ≥60ml/min. The blood coagulation function test should meet the following criteria: prothrombin time (PT), activated partial thromboplastin time (APTT), international standardized ratio (INR) ≤1.5×ULN (no anticoagulant therapy); Cardiac ultrasound evaluation: left ventricular ejection fraction (LVEF)≥50%. Exclusion Criteria: 1 Complicated diseases and medical history: Has had other malignant tumors within 3 years or currently has other malignant tumors; Have a variety of factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction); Unmitigated toxicity above CTCAE1 grade due to any prior treatment; Severe infections (≥CTCAE2 grade) that were active or uncontrolled before the study treatment started; Cirrhosis, active hepatitis； Have a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 2 Tumor-related symptoms and treatment: Clinical evidence or history of central nervous system metastases (CNS) and/or cancerous meningitis or pneumomeningeal disease; Had received chemotherapy within 3 weeks prior to the start of study treatment, and had received radiotherapy (except palliative radiotherapy for non-target lesions), hormone therapy, or other anti-tumor therapy within 2 weeks prior to the start of study treatment (washout period was calculated from the end of last treatment); Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage (as determined by the investigator). 3 Known to be allergic to fluvestone, TQB3616 or any excipient. 4 Participated in clinical trials of other antitumor drugs within 4 weeks prior to the initiation of study therapy. 5 Has other conditions that make it inappropriate for the patient to be enrolled based on investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB3616 capsules plus fulvestrant<br>The dose of TQB3616 capsules is 180mg, taken orally on an empty stomach, once a day for 28 consecutive days as one treatment cycle. Fluvestrin injection was given at a fixed dose of 500mg on day 1, day 15 of the first treatment cycle and day 1 of each subsequent treatment cycle, and a treatment cycle of 28 days. | Drug: TQB3616 capsules<br>* The dose of TQB3616 capsules is 180mg, taken orally on an empty stomach, once a day for 28 consecutive days as one treatment cycle.<br>Drug: Fluvestrin injection<br>* Fluvestrin injection was given at a fixed dose of 500mg on day 1, day 15 of the first treatment cycle and day 1 of each subsequent treatment cycle, and a treatment cycle of 28 days.<br>|
| Placebo Comparator: TQB3616-matching placebo plus fulvestrant<br>The dose of placebo is 180mg, taken orally on an empty stomach, once a day for 28 consecutive days as one treatment cycle. Fluvestrin injection was given at a fixed dose of 500mg on day 1, day 15 of the first treatment cycle and day 1 of each subsequent treatment cycle, and a treatment cycle of 28 days. | Drug: TQB3616-matching placebo<br>* The dose of placebo is 180mg, taken orally on an empty stomach, once a day for 28 consecutive days as one treatment cycle.<br>Drug: Fluvestrin injection<br>* Fluvestrin injection was given at a fixed dose of 500mg on day 1, day 15 of the first treatment cycle and day 1 of each subsequent treatment cycle, and a treatment cycle of 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival (First-time progression of disease/ recurrence /death) | Baseline up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) by Independent Review Committee | Progression-free survival（First-time progression of disease/ recurrence /death） | Baseline up to 24 months | 
| Overall survival (OS) | Overall survival (Baseline up to death) | Baseline up to 24 months | 
| Clinical benefit rate (CBR) | Percentage of subjects with complete (CR) or partial response (PR) or stable disease (SD)（ Baseline up to progression of disease/ recurrence /death） | Baseline up to 24 months | 
| Duration of Response (DOR) | Duration of Response(Baseline up to progression of disease/ recurrence /death) | Baseline up to 24 months |