Clinical trial NCT05775575: A Clinical Trial of TQB3909 Tablets in Patients With Breast Cancer
Official title: A Phase Ib/II Study to Investigate the Safety, Tolerance and Pharmacokinetics of TQB3909 With HR-positive, HER2-negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Breast Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-03-20
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TQB3909 is an inhibitor targeting B-cell lymphoma (BCL)-2 protein. By binding to BCL-2 protein, TQB3909 releases Pro apoptotic proteins such as BCL-2-Anatagonist/Killer 1(BAK), BCL-2 associated X (BAX) protein and BCL-2 associated death (BAD) protein, promotes the release of cytochrome c from mitochondria, phosphatidylserine eversion, stimulates caspase 3/7 activity and caspase 3/9 cleavage, and induces apoptosis.


Eligibility criteria: Inclusion Criteria:

* Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
* Age: 18 to 75 years old; female patient, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Histopathologically confirmed HR positive and HER2 negative advanced or metastatic breast cancer.
* Patients who have been treated with endocrine therapy and have experienced disease progression.
* Patients previously treated with any CDK4/6 inhibitor and not treated with BCL-2 inhibitor.
* Has at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria
* The main organs function well;
* Female patient had no plans to become pregnant and voluntarily took effective contraceptive measures from agree with the study to at least 6 months after the last dose of study drug.

Exclusion Criteria:

* 1. Concomitant disease and medical history:

  1. There were other malignant tumors in 3 years before the first medication.
  2. Has multiple factors affecting oral medication;
  3. Unalleviated toxicity ≥ grade 1 due to any previous therapy;
  4. Major surgical treatment, open biopsy and obvious traumatic injury were performed within 28 days before the study; e．Arteriovenous thrombotic events occurred within 6 months before the first medication, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism; f．Have a history of psychotropic drug abuse and can not quit or have mental disorders; g．Subjects with any severe and / or uncontrolled disease included: Cirrhosis, active hepatitis, history of immunodeficiency;
* Tumor-related symptoms and treatment:

  1. Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis;
  2. have received radiotherapy, other antineoplastic therapy within 2 weeks prior to the first dose;
  3. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
* Known hypersensitivity to TQB3909, LHRH agonists (e.g., goserelin), or any excipients.
* Subjects who have received the vaccine within 28 days prior to the first dose, or are planning to receive the vaccine during the study period.
* Has Participated in other clinical trials within 4 weeks before first dose.
* According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: At the end of Cycle 1 (Cycle 1, Day 28)
measure: Maximum tolerated dose (MTD)
timeFrame: At the end of Cycle 1 (Cycle 1, Day 28)
measure: Recommended Phase II Dose (RP2D)
timeFrame: Baseline up to 24 months
Secondary outcomes:
measure: Time to reach maximum (peak)plasma concentration (Tmax)
timeFrame: before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28.
measure: Peak concentration (Cmax)
timeFrame: before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28.
measure: Terminal half-life (T1/2)
timeFrame: before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28.
measure: Area under the plasma concentration-time curve from time zero to time t (AUC0-t)
timeFrame: before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28.
measure: Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)
timeFrame: before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28.
measure: Minimum steady-state plasma drug concentration during a dosage interval (Cmin,ss)
timeFrame: before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28.
measure: Clinilca Benefit Rate (CBR)
timeFrame: From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks.
measure: Objective Response Rate (ORR)
timeFrame: From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks.
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
References: