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
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
1 other identifier
interventional
432
1 country
88
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2022
Typical duration for phase_3
88 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 26, 2022
CompletedFirst Posted
Study publicly available on registry
May 9, 2022
CompletedStudy Start
First participant enrolled
July 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 2, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
ExpectedJanuary 7, 2026
July 1, 2025
3 years
April 26, 2022
January 4, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival as assessed by the investigator
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.
Baseline up to progressive disease (PD)/die, about 25.8 months
Secondary Outcomes (8)
Progression-free survival (PFS) by independent imaging assessment
Baseline up to PD/die, about 25.8 months
Overall survival
Baseline up to die, about 36months
3-Year Overall Survival (OS)
Baseline to 3 years
Objective Response Rate (ORR)
Baseline to CR/PR，about 1 year
Clinical Benefit Rate(CBR)
Baseline to CR/PR/SD，about 1 year
- +3 more secondary outcomes
Study Arms (2)
TQB3616 capsule + Fulvestrant injection
EXPERIMENTALTQB3616 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 COMPARATORPlacebo 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
Interventions
Fulvestrant is a competitive estrogen receptor antagonist, and its mechanism is related to the down-regulation of estrogen receptor (ER) protein level
TQB3616 capsule is a CDK (cyclin-dependent kinases) 2/4/6 kinase inhibitor, which can selectively inhibit THE activity of CDK2/4/6 kinase, make it form a complex with Cyclin D, reduce the phosphorylation level of retinoblastoma protein (Rb) in cancer cells, and prevent cells from entering S phase from G1 phase
Eligibility Criteria
You may qualify if:
- 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：
- Routine blood examination should meet the following criteria: (No blood transfusion and no hematopoietic stimulation drugs within 7 days before screening)
- Hemoglobin (HB) ≥100 g/L;
- Absolute value of neutrophils (NEUT) ≥ 1.5×109/L;
- Platelet count (PLT) ≥ 90 ×109/L.
- Biochemical blood tests shall meet the following criteria：
- Total bilirubin (TBIL) ≤ 1.5 times normal upper limit (ULN);
- Alanine transferase (ALT) and aspartate transferase (AST) ≤ 2.5×ULN; ALT and AST≤ 3×ULN for patients with liver metastasis;
- Serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance (Ccr) ≥ 60 mL /min；
- Coagulation function tests shall meet the following criteria：
- +3 more criteria
You may not qualify if:
- Associated diseases and history：
- 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor infiltrating basal membrane)\];
- 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);
- Patients with a history of severe pneumonia such as interstitial lung disease;
- 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;
- Major surgery or significant traumatic injury within 28 days prior to randomization;
- Long-term unhealed wounds, ulcers or fractures;
- 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.;
- History of psychotropic drug abuse and can't get rid of it or with mental disorders;
- Subject with any severe and/or uncontrolled disease, including：
- 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;
- Active or uncontrolled severe infection (≥CTCAE grade 2 infection) or unexplained fever \> 38.5℃ within 28 days prior to randomization;
- Decompensated cirrhosis (Child-Pugh liver function score B or C), active hepatitis ;
- Patients with renal failure requiring hemodialysis or peritoneal dialysis;
- 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;
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (88)
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233099, China
The First Affiliated Hospital of Wannan Medical College
Wuhu, Anhui, 241000, China
Peking University First Hospital
Beijing, Beijing Municipality, 100034, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, 400000, China
The Southwest Hospital of AMU
Chongqing, Chongqing Municipality, 400083, China
Fujian Provincial Cancer Hospital
Fuzhou, Fujian, 350014, China
Gansu Provincial Cancer Hospital
Lanzhou, Gansu, 730000, China
Lanzhou University Second Hospital
Lanzhou, Gansu, 730030, China
Gansu Wuwei Tumour Hospital
Wuwei, Gansu, 730000, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510060, China
Nanfang Hospital Southern Medical University
Guangzhou, Guangdong, 510080, China
The Third Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510630, China
Jieyang People's Hospital
Jieyang, Guangdong, 522095, China
Maoming people's hospital
Maoming, Guangdong, 525000, China
Yue Bei People's Hospital
Shaoguan, Guangdong, 512025, China
ShenZhen People's Hospital
Shenzhen, Guangdong, 518020, China
PeKing University ShenZhen Hosipital
Shenzhen, Guangdong, 518036, China
Zhongshan City People's Hospital
Zhongshan, Guangdong, 528403, China
The Fifth Affiliated Hospital of Sun Yat-Sen University
Zhuhai, Guangdong, 519099, China
The Second Affiliated Hospital of Guilin Medical University
Guilin, Guangxi, 541199, China
Yulin First People's Hospital
Yulin, Guangxi, 537000, China
The Affiliated Hospital of Hebei University
Baoding, Hebei, 071000, China
Cangzhou Central Hospital
Cangzhou, Hebei, 061013, China
Hebei Cangzhou Hospital of Integrated Traditional Chinese
Cangzhou, Hebei, 061013, China
Affiliated Hospital of Chengde Medical University
Chengde, Hebei, 067020, China
Hebei Petro China Central Hospital
Langfang, Hebei, 065000, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050011, China
Affiliated Cancer Hospital of Harbin Medical University
Harbin, Heilongjiang, 150081, China
The Second Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150086, China
Jiamusi Cancer Hospital
Jiamusi, Heilongjiang, 154007, China
Luoyang Central Hospital
Luoyang, Henan, 471003, China
Nanyang Central Hospital
Nanyang, Henan, 473000, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Henan Cancer Hospital
Zhengzhou, Henan, 45008, China
Yichang Central People's Hospital
Yichang, Hubei, 443003, China
The First People's Hospital of Changde
Changde, Hunan, 415003, China
The Second Xiangya Hospital of Central South University
Changsha, Hunan, 410000, China
Xiangya Hospital of Central South University
Changsha, Hunan, 410000, China
Hunan Cancer Hospital
Changsha, Hunan, 410031, China
Changzhou Cancer Hospital
Changzhou, Jiangsu, 213000, China
Huai'an First People's Hospital
Huai'an, Jiangsu, 223300, China
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008, China
Jiangsu province hospital
Nanjing, Jiangsu, 210029, China
Affiliated Hospital of Nantong University
Nantong, Jiangsu, 226001, China
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221004, China
The First Affiliated Hospital of Gannan Medical University
Ganzhou, Jiangxi, 341099, China
The Third Hospital of Nanchang
Nanchang, Jiangxi, 330000, China
Jilin Cancer Hospital
Changchun, Jilin, 130012, China
The First Hospital of Jilin University
Changchun, Jilin, 130021, China
Second Hospital of Jilin University
Changchun, Jilin, 130041, China
The Second Hosptial of DaLian Medical University
Dalian, Liaoning, 116000, China
Affiliated Zhongshan Hospital of Dalian University
Dalian, Liaoning, 116001, China
The First Affiliated Hospital of Jinzhou Medical University
Jinzhou, Liaoning, 121012, China
The First Affiliated Hospital of China Medical University
Shenyang, Liaoning, 110002, China
Liaoning Cancer Hospital & Institute
Shenyang, Liaoning, 110042, China
Affiliated Hospital of Chifeng University
Chifeng, Neimenggu, 024005, China
Inner Mongolia Autonomous Region Cancer Hospital
Hohhot, Neimenggu, 010000, China
The Affilliate Hospital of Inner Mongolia Medical Univercity
Hohhot, Neimenggu, 010000, China
General Hospital of Ningxia Medical
Yinchuan, Ningxia, 750003, China
Qinghai University affiliated hospital
Xining, Qinghai, 810000, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710000, China
First Affiliated University Hospital of PLA Air Force Military Medical
Xi'an, Shaanxi, 710032, China
Second Affiliated Hospital of PLA Air Force Military Medical
Xi'an, Shaanxi, 710038, China
Xi'an International Medical Center Hospital
Xi'an, Shaanxi, 710100, China
Binzhou Medical College Affiliated Hospital
Binzhou, Shandong, 256699, China
Shandong Cancer Hospital
Jinan, Shandong, 250117, China
Affiliated Hospital of Jining Medical University
Jining, Shandong, 272000, China
Linyin Cancer Hospital
Linyi, Shandong, 276000, China
Qingdao University Affiliated Hospital
Qingdao, Shandong, 266071, China
Weifang Hospital of Traditional Chinese Midicine
Weifang, Shandong, 261000, China
Yantai Yantai Mountain hospital
Yantai, Shandong, 264008, China
Zibo Central Hospital
Zibo, Shandong, 255020, China
Huadong Hospital
Shanghai, Shanghai Municipality, 200040, China
Shanghai Oriental Hospital
Shanghai, Shanghai Municipality, 200123, China
Shanghai Changhai Hospital
Shanghai, Shanghai Municipality, 200433, China
Changzhi People's Hospital
Changzhi, Shanxi, 046000, China
Shanxi Cancer Hospital
Taiyuan, Shanxi, 030013, China
Chinese People's Liberation Army Western Theater General Hospital
Chengdu, Sichuan, 610083, China
The Affiliated Hospital of Southwest Medical University
Luzhou, Sichuan, 646000, China
Suining Central Hospital
Suining, Sichuan, 629000, China
Tianjin Medical University Cancer Hospital
Tianjin, Tianjin Municipality, 300060, China
Tianjin Medical University Cancer Hospital Konggang Hospital
Tianjin, Tianjin Municipality, 300308, China
Cancer Hospital affiliated to Xinjiang Medical University
Ürümqi, Xinjiang, 830011, China
Yunnan Cancel Hospital
Kunming, Yunan, 650106, China
Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medcine
Hangzhou, Zhejiang, 310006, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
Related Publications (1)
Xu Z, Liu Y, Song B, Ren B, Xu X, Lin R, Zhu X, Chen C, Yang S, Zhu Y, Jiang W, Li W, Xia Y, Hu L, Chen S, Chan CC, Li J, Zhang X, Yang L, Tian X, Ding CZ. Discovery and preclinical evaluations of TQB3616, a novel CDK4-biased inhibitor. Bioorg Med Chem Lett. 2024 Jul 15;107:129769. doi: 10.1016/j.bmcl.2024.129769. Epub 2024 Apr 24.
PMID: 38670537DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 26, 2022
First Posted
May 9, 2022
Study Start
July 1, 2022
Primary Completion
July 2, 2025
Study Completion (Estimated)
June 1, 2026
Last Updated
January 7, 2026
Record last verified: 2025-07