Clinical trial NCT06851442: Clinical Trial of Evaluating TQB3912 Tablets Combined With Fulvestrant Injection±TQB3616 Capsules for Locally Advanced or Metastatic Hormone Receptor(HR)-Positive and Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
Official title: A Phase Ib/II Clinical Trial to Evaluate the Efficacy and Safety of TQB3912 Tablets in Combination With Fulvestrant Injection± TQB3616 Capsules in Patients With Locally Advanced or Metastatic HR-positive and HER2-negative Breast Cancer.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-02-28
Enrollment: 75
Sex: ALL
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: This trial was designed to evaluate the maximum tolerated dose (MTD) and phase II recommended dose (RP2D) in subjects with TQB3912 tablets combined with fulvestrant injection and TQB3616 capsules for locally advanced or metastatic HR-positive and HER2-negative breast cancer.And the effectiveness of TQB3912 tablets combined with fulvestrant injection ±TQB3616 capsules in locally advanced or metastatic HR-positive and HER2-negative breast cancer subjects was evaluated by evaluating ORR, PFS, DOR, DCR, CBR, OS, etc., and at the same time, Assess its safety and pharmacokinetic (PK) characteristics.


Eligibility criteria: Inclusion Criteria:

* The subjects voluntarily joined the study, signed an informed consent form, and had good compliance.
* Age: 18-75 years old; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score: 0\~1 point; estimated survival time exceeds 3 months.
* Women can be in the late period of menopause and before menopause/innerspring. If they are before menopause/siege period, they must continue to receive ovarian function inhibitory treatment during the research period to enter the group.
* Anthropologically confirmed HR-positive and HER2-negative breast cancer.
* Locally advanced or metastatic diseases that cannot undergo radical surgery.
* Queue 1 Previous treatment requirements: progress after endocrine therapy; Queue 2 Previous treatment requirements: progress after endocrine therapy.
* Have one or more phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)/v-akt murine thymoma viral oncogene homolog 1 (AKT1)/phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene mutations.
* At least one measurable lesion exists according to the RECIST 1.1 standard.
* Good function of the main organs
* Female subjects of childbearing age should agree that contraceptive measures (such as Buds, contraceptives or condoms) must be used during the study period and within 6 months after the study ends; the serum pregnancy test is negative within 7 days before the study enrollment. , and must be non-lactation subjects; male subjects should agree to adopt contraceptive measures within 6 months after the end of the study period.

Exclusion Criteria:

* It is known to suffer from spinal cord compression, cancerous meningitis, symptoms with brain metastasis or symptoms control for less than 4 weeks.
* Combined diseases and medical history:

  1. Have appeared within 3 years or have also suffered from other malignant tumors;
  2. Adverse reactions from previous treatments have not been restored to CTCAE 5.0 grade≤1;
  3. It affects oral and drug absorption
  4. Those who have received major surgical treatment within 4 weeks before the first medication, obvious traumatic injury or expected to undergo major surgery during the study treatment, or have long-term uncured wounds or fractures;
  5. Congenital bleeding , coagulation dysfunction disease;
  6. Arterial/deep thrombosis events occurred;
  7. Blood pressure control was not ideal;
  8. Major cardiovascular disease;
  9. Uncontrolled ≥CTCAE level 2 within 14 days before the start of study treatment
  10. A history of active tuberculosis, pulmonary fibrosis or pneumonia;
  11. a past or currently associated with interstitial lung disease/pneumonia;
  12. active viral hepatitis and poor control;
  13. treatment is required
  14. uncontrollable kidney disease;
  15. a history of immunodeficiency;
  16. a person who is prepared to undergo or has undergone genealogical bone marrow transplants or solid organ transplants;
  17. uncontrollable diabetes;
  18. a person who suffers from People with epilepsy and need treatment;
  19. People with a history of psychotropic substance abuse and cannot be abstained or have mental disorders.
* Tumor-related symptoms and treatment:

  1. If it is not controlled, the third gap effusion still needs to be repeatedly drained;
  2. There is lung cancer pharyngitis;
  3. During the study period, the tumor is very likely to invade important blood vessels and cause it Fatal severe bleeding;
  4. Use strong CYP3A4 inhibitor or strong inducer, and the drug half-life is less than 3 before the start of the study treatment;
  5. Have received anti-tumor treatment within 3 weeks before the start of the study treatment, and the washing is calculated from the end of the last treatment
  6. Within 2 weeks before the start of the study treatment, Chinese patent medicine treatment with anti-tumor indications was received in the National Medical Products Administration (NMPA) approved drug instructions.
* Research and treatment related:

  1. Used phosphatidylinositol 3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) inhibitors;
  2. Used fulvestrant or other selective estrogen receptor degrading agents (SERD);
  3. Used in any study drug or drug Allergic to any ingredient or excipient;
  4. a history of live attenuated vaccination within 28 days before the first medication or planned to undergo live attenuated vaccination during the study period;
  5. is receiving systemic glucocorticoid therapy or any other form of immunosuppression therapy, and Continued use within 2 weeks before the start of the study treatment
* According to the judgment of the researcher, there are situations that seriously endanger the safety of the subject or affect the subject's completion of the research.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: 4 months after Queue 2 begins enrollment
measure: phase II recommended dose (RP2D)
timeFrame: 4 months after Queue 2 begins enrollment
measure: Objective Remission Rate (ORR)
timeFrame: 8 to 16 weeks after enrollment
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From enrollment to disease progression, an average of 14 months
measure: Duration of response (DOR)
timeFrame: From enrollment to disease progression, an average of 14 months
measure: Disease control rate (DCR)
timeFrame: 8 to 16 weeks after enrollment
measure: Clinical benefit ratio (CBR)
timeFrame: ≥24 weeks after enrollment
measure: Overall survival (OS)
timeFrame: From enrollment to subject death, it is expected to be evaluated until 5 years
measure: Number of patients with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Within 28 days after dosing
measure: Peak time (Tmax)
timeFrame: Within 24 hours after dosing
measure: Peak concentration (Cmax)
timeFrame: 30 minuets pre-dose at cycle 1 day 1, 8 and day 28. 30 minuets,1, 2, 3, 4, 6, 8, 12, 24 hours after dose at cycle 1 day 1 and day 28. Each cycle is 28 days
measure: Elimination half life (t1/2)
timeFrame: Within 1～7 days after dose
measure: Area under plasma concentration-time curve (AUC0-∞)
timeFrame: Within 28 days after dosing
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Fuzhou
country: China
facility: Fuzhou First General Hospital
state: Fujian
city: Quanzhou
country: China
facility: Quanzhou First Hospital
state: Fujian
city: Meizhou
country: China
facility: Meizhou peoples Hospital
state: Guangdong
city: Guiyang
country: China
facility: Guizhou Medical University Affiliated Cancer Hospital Co., Ltd
state: Guizhou
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Harbin
country: China
facility: Harbin Medical University Cancer
state: Heilongjiang
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Yongzhou
country: China
facility: Yongzhou Central Hospital
state: Hunan
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiao Tong University
state: Shaanxi
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Cancer Hospital Airport Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Xinjiang Medical University Affiliated Cancer Hospital
state: Xinjiang
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Central Hospital (Taizhou University Affiliated Hospital)
state: Zhejiang
Study officials:
References: