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

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

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.

Study Overview

• Status: Completed
• Conditions: HR-positive,HER2-negative in Advanced Breast Cancer
• Intervention / Treatment: Drug: TQB3616 capsules; Drug: Fluvestrin injection; Drug: TQB3616-matching placebo

• Study Type: Interventional
• Enrollment (Actual): 293
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100039
      • The Fifth Medical Center of PLA General Hospital
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hosptital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. Has had other malignant tumors within 3 years or currently has other malignant tumors;
  2. Have a variety of factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction);
  3. Unmitigated toxicity above CTCAE1 grade due to any prior treatment;
  4. Severe infections (≥CTCAE2 grade) that were active or uncontrolled before the study treatment started;
  5. Cirrhosis, active hepatitis；
  6. 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:

  1. Clinical evidence or history of central nervous system metastases (CNS) and/or cancerous meningitis or pneumomeningeal disease;
  2. 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);
  3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQB3616 capsules plus fulvestrant; 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; The dose of TQB3616 capsules is 180mg, taken orally on an empty stomach, once a day for 28 consecutive days as one treatment cycle.; Drug: Fluvestrin injection; 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.
Placebo Comparator: TQB3616-matching placebo plus fulvestrant; 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: Fluvestrin injection; 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; The dose of placebo is 180mg, taken orally on an empty stomach, once a day for 28 consecutive days as one treatment cycle.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Publications and helpful links

General Publications

• 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.
• Yin Y, Zhang Q, Sun T, Hao C, Wang Z, Yang J, Wang Y, Shi Y, Sun J, Ouyang Q, Su H, Wu J, Gan L, Han M, Gao L, Wang X, Zhao B, Li H, Zhao J, Yang H, Ning F, Tian F, Zhang J, Sun H, Niu Z, Zong H, Zang A, Wang X, Qian X, Wu S, Nie J, He L, Cheng Y, Hao Y, Zhai Y, Li H, Wang J, Wei S, Li M, Liu Y, Guo H, Hu Q, Liu L, Han X, Luo R, Ni M, Tang X, Zhai Z, Ding M, Wang H, Shen P, Wang X, Liu L, Chen W, Liu G, Cai Z, Jiang Z. Novel CDK2/4/6 inhibitor culmerciclib (TQB3616) plus fulvestrant in previously treated, HR-positive, HER2-negative advanced breast cancer: a randomized, double-blind, phase 3 trial. Signal Transduct Target Ther. 2025 Dec 18;10(1):414. doi: 10.1038/s41392-025-02475-6.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Actual): January 16, 2024
• Study Completion (Actual): December 9, 2025

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: TQB3616-III-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No