To Evaluate the Efficacy and Safety of TQB3616 in Combination With Fulvestrant Versus Placebo in Combination With Fulvestrant in Previously Untreated Hormone-receptor (HR)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced Breast Cancer

Phase 3

Active, not recruiting

• Conditions: HR-positive, HER2-negative Breast Neoplasms
• Interventions: Drug: TQB3616 capsule; Drug: Placebo; Drug: Fulvestrant injection

• Registration Number: NCT05365178
• Lead Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary

A randomized, double-blind, parallel-controlled, multicenter trial design was used in this study. Subjects who meet the criteria will be randomly divided into 2:1 groups to receive TBQ3616 capsule combined with Fulvestrant injection (experimental group) or placebo capsule combined with fulvestrant (control group). A total of 428 subjects were required.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-26
• Study First Submitted QC: 2022-05-06
• Study First Posted: 2022-05-09
• Study Start: 2022-07-01
• Status Verified: 2025-07
• Primary Completion: 2025-07-02
• Last Update Submitted: 2025-07-02
• Last Update Posted: 2025-07-03
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 432

Inclusion Criteria

• Subjects voluntarily participate in this study and sign informed consent with good compliance;

• Age: 18-75 years (when signing the informed consent); an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Is expected to survive more than 3 months;

• Postmenopausal or premenopausal/perimenopausal women；

• Patients with HR-positive or HER2-negative breast cancer confirmed by pathological examination with evidence of local lesion recurrence or distant metastasis, not suitable for the surgery or radiotherapy for the purpose of cure, and there are no clinical indications of chemotherapy；

• Have a measurable lesion (RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria), or have only bone metastases；

• The main organs function well and meet the following standards：

  1. Routine blood examination should meet the following criteria: (No blood transfusion and no hematopoietic stimulation drugs within 7 days before screening)

     1. Hemoglobin (HB) ≥100 g/L;
     2. Absolute value of neutrophils (NEUT) ≥ 1.5×109/L;
     3. Platelet count (PLT) ≥ 90 ×109/L.

  2. Biochemical blood tests shall meet the following criteria：

     1. Total bilirubin (TBIL) ≤ 1.5 times normal upper limit (ULN);
     2. Alanine transferase (ALT) and aspartate transferase (AST) ≤ 2.5×ULN; ALT and AST≤ 3×ULN for patients with liver metastasis;
     3. Serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance (Ccr) ≥ 60 mL /min；

  3. Coagulation function tests shall meet the following criteria：

     (a) Prothrombin time (PT), activated partial thrombin time (APTT), international standardized

  4. Color doppler echocardiography: Left ventricular ejection fraction (LVEF) ≥50%；

• Female subjects within reproductive age should agree to use contraceptive methods (such as intrauterine devices, birth control pills or condoms) from participating the study to 6 months after the end of the study; Serum pregnancy test result should be negative within 7 days prior to study enrollment and must be non-lactating subjects.

Exclusion Criteria

• Associated diseases and history：

  1. The presence or current co-occurrence of other malignant tumors within 5 years, except ured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor infiltrating basal membrane)];

  2. Multiple factors affecting oral and drug absorption (such as inability to swallow, post-gastrointestinal resection, ulcerative colitis, symptomatic/inflammatory bowel disease, chronic diarrhea and intestinal obstruction);

  3. Patients with a history of severe pneumonia such as interstitial lung disease;

  4. Unrelieved toxicity higher than GRADE 1 Common Terminology Criteria for Adverse Events (CTCAE) due to any previous anti-tumor treatment, hair loss is not included;

  5. Major surgery or significant traumatic injury within 28 days prior to randomization;

  6. Long-term unhealed wounds, ulcers or fractures;

  7. Occurrence of arteriovenous/venous thrombosis events within 6 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;

  8. History of psychotropic drug abuse and can't get rid of it or with mental disorders;

  9. Subject with any severe and/or uncontrolled disease, including：

     1. Arrhythmias requiring treatment with grade≥2 myocardial ischemia, myocardial infarction, and congestive heart failure (NYHA(New York Heart Association) classification) within 6 months prior to study enrollment (including qtc≥480ms during screening period); And uncontrolled high blood pressure;
     2. Active or uncontrolled severe infection (≥CTCAE grade 2 infection) or unexplained fever > 38.5℃ within 28 days prior to randomization;
     3. Decompensated cirrhosis (Child-Pugh liver function score B or C), active hepatitis ;
     4. Patients with renal failure requiring hemodialysis or peritoneal dialysis;
     5. A history of immunodeficiency, including HIV ( Human Immunodeficiency Virus) positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or hematopoietic stem cell transplantation;

• Tumor-related symptoms and treatment；

  1. Visceral crisis exists;
  2. Severe bone injury due to bone metastasis of tumor;
  3. Received radiotherapy (except palliative radiotherapy for non-target lesions) and other anti-tumor therapies (the washout period was calculated from the end of the last treatment) within 2 weeks prior to randomization;
  4. Prior medical treatment with fulvestrant, everolimus or CDK4/6 inhibitor;
  5. The presence of clinically uncontrolled pleural, ascites and pericardial effusion requiring repeated drainage or medical intervention (14 days prior to randomization);

• Known allergy to fulvestrant, Luteal Hormone Releasing Hormone (LHRH) agonists (e.g. Goserelin), TQB3616/ placebo or any supplement;

• History of live attenuated vaccine vaccination within 28 days prior to randomization or planned live attenuated vaccine vaccination during the study period;

• Participated in clinical trials of other antitumor drugs within 4 weeks pior to randomization;

• With other serious physical or mental diseases or abnormal laboratory tests that may increase the risk of study participation or interfere with the study results, or unsuitable for the study for other reasons considered by investigators.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TQB3616 capsule + Fulvestrant injection	TQB3616 capsule	TQB3616 capsule: 180mg was given orally with meals or within 2 hours after meals, once a day， every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15
TQB3616 capsule + Fulvestrant injection	Fulvestrant injection	TQB3616 capsule: 180mg was given orally with meals or within 2 hours after meals, once a day， every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15
Placebo capsule + Fulvestrant injection	Placebo	Placebo capsules: 0mg was given orally with meals or within 2 hours after meals, once a day, every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15
Placebo capsule + Fulvestrant injection	Fulvestrant injection	Placebo capsules: 0mg was given orally with meals or within 2 hours after meals, once a day, every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15

Primary Outcome Measures

Name	Time	Method
Progression-free survival as assessed by the investigator	Baseline up to progressive disease (PD)/die, about 25.8 months	The time from enrollment to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) by independent imaging assessment	Baseline up to PD/die, about 25.8 months	The time from enrollment to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.
Objective Response Rate (ORR)	Baseline to CR/PR，about 1 year
Duration of Overall Response (DOR)	CR/PR assessment, up to PD/die, about 20 months	The time from the date of participants with a first overall response defined as complete response (CR) or partial response (PR) to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.
The European Organization for Research and Treatment of Cancer Quality of Life questionnaire	Baseline to the end of the study, about 3 years	Sense of satisfaction, life quality of participants since the enrollment of the study
Incidence of adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs).	Baseline to the end of the study, about 3 years	The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs).
Overall survival	Baseline up to die, about 36months	Overall survival was defined as the time from randomization to death from any cause.
3-Year Overall Survival (OS)	Baseline to 3 years	The percentage of participants of survival above 3 years
Clinical Benefit Rate(CBR)	Baseline to CR/PR/SD，about 1 year	Calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD).

Trial Locations

Locations (88)

The First Affiliated Hospital of Bengbu Medical College; 🇨🇳 Bengbu, Anhui, China

The First Affiliated Hospital of Wannan Medical College; 🇨🇳 Wuhu, Anhui, China

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China

The Southwest Hospital of AMU; 🇨🇳 Chongqing, Chongqing, China

Fujian Provincial Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

Gansu Provincial Cancer Hospital; 🇨🇳 Lanzhou, Gansu, China

Lanzhou University Second Hospital; 🇨🇳 Lanzhou, Gansu, China

Gansu Wuwei Tumour Hospital; 🇨🇳 Wuwei, Gansu, China

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