Clinical trial NCT05365178: 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
Official title: A Randomized, Double-blind, Parallel-controlled Phase III Trial Evaluating the Efficacy and Safety of TQB3616 in Combination With Fulvestrant Versus Placebo in Combination With Fulvestrant in Previously Untreated HR-positive, HER2-negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HR-positive, HER2-negative Breast Neoplasms
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-05-09
Enrollment: 432
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival as assessed by the investigator
timeFrame: Baseline up to progressive disease (PD)/die, about 25.8 months
Secondary outcomes:
measure: Progression-free survival (PFS) by independent imaging assessment
timeFrame: Baseline up to PD/die, about 25.8 months
measure: Overall survival
timeFrame: Baseline up to die, about 36months
measure: 3-Year Overall Survival (OS)
timeFrame: Baseline to 3 years
measure: Objective Response Rate (ORR)
timeFrame: Baseline to CR/PR，about 1 year
measure: Clinical Benefit Rate(CBR)
timeFrame: Baseline to CR/PR/SD，about 1 year
measure: Duration of Overall Response (DOR)
timeFrame: CR/PR assessment, up to PD/die, about 20 months
measure: The European Organization for Research and Treatment of Cancer Quality of Life questionnaire
timeFrame: Baseline to the end of the study, about 3 years
measure: Incidence of adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs).
timeFrame: Baseline to the end of the study, about 3 years
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Wuhu
country: China
facility: The First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: The Southwest Hospital of AMU
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Wuwei
country: China
facility: Gansu Wuwei Tumour Hospital
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Jieyang
country: China
facility: Jieyang People's Hospital
state: Guangdong
city: Maoming
country: China
facility: Maoming people's hospital
state: Guangdong
city: Shaoguan
country: China
facility: Yue Bei People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: ShenZhen People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: PeKing University ShenZhen Hosipital
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan City People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guilin
country: China
facility: The Second Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Yulin
country: China
facility: Yulin First People's Hospital
state: Guangxi
city: Baoding
country: China
facility: The Affiliated Hospital of Hebei University
state: Hebei
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Cangzhou
country: China
facility: Hebei Cangzhou Hospital of Integrated Traditional Chinese
state: Hebei
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical University
state: Hebei
city: Langfang
country: China
facility: Hebei Petro China Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Jiamusi
country: China
facility: Jiamusi Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Yichang
country: China
facility: Yichang Central People's Hospital
state: Hubei
city: Changde
country: China
facility: The First People's Hospital of Changde
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changzhou
country: China
facility: Changzhou Cancer Hospital
state: Jiangsu
city: Huai'an
country: China
facility: Huai'an First People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu province hospital
state: Jiangsu
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Ganzhou
country: China
facility: The First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Nanchang
country: China
facility: The Third Hospital of Nanchang
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Second Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The Second Hosptial of DaLian Medical University
state: Liaoning
city: Dalian
country: China
facility: Affiliated Zhongshan Hospital of Dalian University
state: Liaoning
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Chifeng
country: China
facility: Affiliated Hospital of Chifeng University
state: Neimenggu
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region Cancer Hospital
state: Neimenggu
city: Hohhot
country: China
facility: The Affilliate Hospital of Inner Mongolia Medical Univercity
state: Neimenggu
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical
state: Ningxia
city: Xining
country: China
facility: Qinghai University affiliated hospital
state: Qinghai
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: First Affiliated University Hospital of PLA Air Force Military Medical
state: Shaanxi
city: Xi'an
country: China
facility: Second Affiliated Hospital of PLA Air Force Military Medical
state: Shaanxi
city: Xi'an
country: China
facility: Xi'an International Medical Center Hospital
state: Shaanxi
city: Binzhou
country: China
facility: Binzhou Medical College Affiliated Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Linyi
country: China
facility: Linyin Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao University Affiliated Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang Hospital of Traditional Chinese Midicine
state: Shandong
city: Yantai
country: China
facility: Yantai Yantai Mountain hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Huadong Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Oriental Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Changzhi
country: China
facility: Changzhi People's Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: Chinese People's Liberation Army Western Theater General Hospital
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Hospital Konggang Hospital
state: Tianjin
city: Urumqi
country: China
facility: Cancer Hospital affiliated to Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancel Hospital
state: Yunan
city: Hangzhou
country: China
facility: Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medcine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: