Clinical Study on Adjuvant Therapy of TQB3616 Combined With Endocrine Therapy Compared With Placebo Combined With Endocrine Therapy in Patients With Breast Cancer

Randomized, Double-blind, Parallel-controlled Phase III Trial to Evaluate the Efficacy and Safety of TQB3616 Combined With Endocrine Therapy Versus Placebo Combined With Endocrine Therapy in Hormone Receptors (HR)-Positive and Human Epidermal GrowthFactor Receptor-2 (HER2) -Negative Breast Cancer Adjuvant Therapy

This is a Phase III, randomized, double-blind, parallel, multi-center trail to evaluate the efficacy and safety of TQB3616 capsule combined with endocrine compared to placebo compared with endocrine in HR-positive and HER2-negative breast cancer adjuvant therapy. Approximately 1946 female subjects will be randomized to either TQB3616 combined with endocrine group or TQB3616-matching placebo combined endocrine group. Randomization will follow a 2:1 ratio, 1297 subjects in experimental group and 649 in the the Placebo Comparator group.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: TQB3616 capsules, Letrozole, Anastrozole, Tamoxifen; Drug: Placebo capsules, Letrozole, Anastrozole, Tamoxifen

• Study Type: Interventional
• Enrollment (Anticipated): 1946
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Science
      • Contact: Binghe Xu, Doctor; Phone Number: +86 13501028690; Email: xubinghe@medmail.com.cn
  • Guangdong
    • Guangzhou, Guangdong, China, 300020
      • Not yet recruiting
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
      • Contact: Qiang Liu, Doctor; Phone Number: +86 18922182851; Email: liuqiang_sysu@163.com
  • Sichuan
    • Suining, Sichuan, China, 629099
      • Recruiting
      • Suining Central Hospital
      • Contact: Hongwei Yang, Master; Phone Number: +86 18008258079; Email: snsyhw@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The subjects voluntarily joined the study and signed the informed consent, with good compliance.
• Age: 18-75 years old (upon signing the informed consent); Eastern Cooperative Oncology Group Performance Status (PS) score: 0~1;
• Surgical treatment of radical mastectomy;
• Pathological examination confirmed HR positive and HER2 negative invasive breast cancer;

• The major organs are functioning well, meeting the following criteria：

  1. Blood biochemical tests should meet the following criteria (no corrective therapy has been used within 7 days prior to screening)：

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

  2. Blood biochemical tests should meet the following criteria (no corrective therapy has been used within 7 days prior to screening)：

     1. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN)；
     2. Alanine transferase (ALT) and aspartate transferase (AST) ≤ 1.5×ULN；
     3. Serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance (Ccr) ≥ 60 ml/min；

  3. Blood clotting tests must meet the following criteria (no anticoagulant therapy)：

     1. Prothrombin time (PT) ≤ 1.5×ULN;
     2. Activated partial thromboplastin time (APTT) ≤ 1.5×ULN;
     3. International Normalized ratio (INR) ≤ 1.5×ULN.
  4. Left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria:

• Complicated diseases and medical history:

  1. Has had other malignant tumors within 5 years or currently has other malignant tumors;
  2. Have a variety of factors that affect oral medication (such as inability to swallow);
  3. Current history of serious lung disease such as interstitial pneumonia；
  4. Severe infections common terminology criteria for adverse events (≥CTCAE (common terminology criteria for adverse events) 2 grade) that were active or uncontrolled before the study treatment started (Except hair loss and hemoglobin)；
• Known allergy to aromatase inhibitors, tamoxifen, TQB3616/ placebo, or any excipients;
• There was a history of live attenuated vaccine vaccination within 28 days prior to randomization or live attenuated vaccine vaccination was planned during the study period;
• Participated in clinical trials of other antitumor agents within 4 weeks prior to randomization；
• The presence of other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of study participation or interfere with the study results, as well as subjects who are deemed unsuitable for study participation for other reasons by the investigator.

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 combined with endocrine; The dose of TQB3616 capsules is 180mg, taken orally when fasting, once a day for 28 consecutive days as one treatment cycle. The dose of Letrozole is 2.5mg, taken orally, once a day for 28 consecutive days as one treatment cycle. The dose of Anastrozole is 1mg, taken orally, once a day for 28 consecutive days as one treatment cycle. The dose of Tamoxifen is 10mg, taken orally, twice a day for 28 consecutive days as one treatment cycle.	Drug: TQB3616 capsules, Letrozole, Anastrozole, Tamoxifen; TQB3616 is a novel Cyclin-dependent kinase (CDK) 4/6 inhibitor and currently being used in the treatment of a variety of malignant solid tumors. Letrozole combined with Anastrozole and Tamoxifen is an endocrine therapy that involves adding, blocking, or removing hormones. It can be used for conditions that affect hormone levels, such as breast cancer.
Placebo Comparator: placebo combined with endocrine; The dose of placebo is 180mg, taken orally when fasting, once a day for 28 consecutive days as one treatment cycle. The dose of Letrozole is 2.5mg, taken orally, once a day for 28 consecutive days as one treatment cycle. The dose of Anastrozole is 1mg, taken orally, once a day for 28 consecutive days as one treatment cycle. The dose of Tamoxifen is 10mg, taken orally, twice a day for 28 consecutive days as one treatment cycle.	Drug: Placebo capsules, Letrozole, Anastrozole, Tamoxifen; Letrozole combined with Anastrozole and Tamoxifen is an endocrine therapy that involves adding, blocking, or removing hormones. It can be used for conditions that affect hormone levels, such as breast cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive Disease-Free Survival (IDFS)	The time from the date of randomization to the first occurrence of the following events, including ipsilateral or contralateral recurrence of invasive breast cancer, regional or distant recurrence of invasive breast cancer, secondary primary malignancy outside the breast, and death from any cause.	Baseline up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The time from first administration to death of any cause.	Baseline up to 60 months
Disease Relapse Free Survival (DRFS)	The time from the date of randomization to the first occurrence of distant recurrence or death from any cause.	Baseline up to 60 months
Incidence of adverse events	Incidence of adverse events assessed according to the common terminology criteria for adverse events (CTCAE).	Baseline up to 60 months
Severity of adverse events	Severity of adverse events assessed according to the common terminology criteria for adverse events (CTCAE).	Baseline up to 60 months
Incidence of abnormal laboratory test values	Incidence of abnormal laboratory test values assessed according to the common terminology criteria for adverse events (CTCAE).	Baseline up to 60 months
Severity of abnormal laboratory test values	Severity of abnormal laboratory test values assessed according to the common terminology criteria for adverse events (CTCAE).	Baseline up to 60 months
Incidence of serious adverse events	Incidence of serious adverse events assessed according to the common terminology criteria for adverse events (CTCAE).	Baseline up to 60 months
Severity of serious adverse events	Severity of serious adverse events assessed according to the common terminology criteria for adverse events (CTCAE).	Baseline up to 60 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Anticipated): December 1, 2026
• Study Completion (Anticipated): January 1, 2027

Study Registration Dates

• First Submitted: March 10, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 19, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen; Anastrozole
• Other Study ID Numbers: TQB3616-III-03

Drug and device information, study documents

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