Clinical trial NCT06561607: A Clinical Trial to Evaluate the Efficacy and Safety of TQB2102 for Injection Versus Investigator-Selected Chemotherapy in HER2 Low-Expressing Recurrent/Metastatic Breast Cancer
Official title: A Randomized, Open, Parallel-Controlled Phase III Clinical Trial Evaluating the Efficacy and Safety of TQB2102 for Injection Versus Investigator-Selected Chemotherapy in HER2 Low-Expressing Recurrent/Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-20
Enrollment: 542
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a Phase III, randomized, multicenter, open-label study in HER2-low, HR+ metastatic breast cancer subjects who are patients with locally advanced or metastatic breast cancer with low HER2 expression in the recurrent metastatic stage who have not received chemotherapy. The primary objective of the study is to determine the efficacy and safety of TQB2102 compared to investigator-selected single-agent chemotherapy in the target population. 542 subjects with HER2 immunohistochemistry (IHC )2+/ in situ hybridization (ISH)- and IHC 1+ (HER2-low) expression will be enrolled in 1:1 randomized groups to receive TQB2102 or investigator's choice of single-agent chemotherapy (capecitabine, paclitaxel, or albumin-paclitaxel) until progression of disease (PD), as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1. 1, unless there are unacceptable toxicity, withdrawal of consent, or meeting other discontinuation criteria.


Eligibility criteria: Inclusion Criteria:

* Subjects voluntarily enrolled in this study with good compliance;
* Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-1;
* Pathologically confirmed locally advanced or metastatic breast cancer with low HER2 expression and unresectable:
* Defined hormone receptor (HR) status.
* Imaging-confirmed disease progression (during or after completion of the most recent treatment);
* Have at least one measurable lesion according to RECIST 1.1 criteria;
* Good major organ function.

Exclusion Criteria:

* The presence or current concurrent presence of other malignant tumors within 5 years prior to randomization. ;
* Unresolved toxic reactions above Common Terminology Criteria for Adverse Events (CTC AE) grade 1 due to any prior therapy;
* Major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of the pre-randomization period;
* Prolonged unhealed wounds or fractures;
* Previous history of interstitial lung disease/pneumonia requiring steroidal drug intervention;
* The presence of moderate to severe pulmonary dysfunction/disease within 3 months prior to randomization;
* The presence of an arterial/deep vein thrombotic event within 6 months prior to randomization;
* The presence of a medical condition that interferes with intravenous administration, intravenous blood collection, or inability to swallow, chronic diarrhea, intestinal obstruction, or the presence of other factors that interfere with the administration and absorption of medications;
* The presence of grade ≥2 myocardial ischemia or myocardial infarction, cardiac arrhythmias (including QT corrected (QTc) ≥450ms (men) and QTc ≥470ms (women)) and grade ≥2 congestive heart failure (New York Heart Association (NYHA) classification); angina pectoris requiring antianginal medication; and clinically significant heart valve disease;
* Active or uncontrolled ≥ CTC AE grade 2 infection present within 14 days prior to randomization;
* Cirrhosis of the liver, active hepatitis that is not well controlled;
* Renal failure requiring hemodialysis or peritoneal dialysis;
* History of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
* Those with routine urinalysis suggestive of urinary protein ≥++ and confirmed 24-hour urine protein quantification \>1.0 g;
* Those who have used immunosuppressive or systemic hormone therapy for immunosuppression within 2 weeks prior to randomization;
* Those with a history of psychotropic substance abuse that cannot be abstained from or those with psychiatric disorders;
* Tumor-related symptoms and treatments:

  1. Subjects who have been treated with other antineoplastic agents such as chemotherapy, radical radiotherapy, or immunotherapy within 4 weeks prior to randomization, or who are still within 5 half-lives of the drug (whichever occurs shortest);
  2. Treatment with endocrine therapy, molecularly targeted therapy, or a proprietary Chinese medicine with an anti-tumor indication as specified in the National Medical Products Administration (NMPA) approved drug insert within 2 weeks prior to randomization;
  3. Presence of carcinomatous lymphadenitis, or uncontrollable pleural effusion, ascites, and pericardial effusion of moderate volume or greater that requires repeated drainage to relieve clinical symptoms, or who have received drainage of plasmapheresis for therapeutic purposes within 2 weeks prior to randomization;
  4. Known carcinomatous meningitis or clinically active central nervous system metastases;
  5. Severe bone damage resulting from tumor bone metastases;
* Those who have received a control chemotherapeutic agent of the investigator's choice during the recurrent metastatic phase or for whom a control chemotherapeutic agent of the investigator's choice is inappropriate for reasons such as intolerance or contraindication to that agent;
* Has received prior anti-HER2 therapy;
* Who have developed hypersensitivity to humanized monoclonal antibody products;
* Those who have developed an allergy to any of the study drugs or any component or excipient in the drugs;
* Who have participated in and used another antitumor clinical trial drug within 4 weeks prior to randomization;
* Subjects who, in the judgment of the investigator, have a concomitant disease that seriously jeopardizes the safety of the subject or interferes with the completion of the study, or who are deemed to have other reasons for being unsuitable for enrollment.

Primary outcomes:
measure: Progression-free survival (PFS) in subjects with HR-positive, HER2 low-expressing recurrent/metastatic breast cancer as assessed by Independent Review Committee (IRC)
timeFrame: Up to 25 months
Secondary outcomes:
measure: Progression-free survival (PFS) in subjects with HER2 low-expressing recurrent/metastatic breast cancer as assessed by IRC
timeFrame: Up to 25 months
measure: Progression-free survival (PFS) as assessed by investigators in the HR-positive, HER2 low-expressing population
timeFrame: Up to 25 months
measure: Investigator-assessed overall survival (OS) in HR-positive, low HER2-expressing population.
timeFrame: Up to 25 months
measure: Overall survival (OS) as assessed by investigators in the HR-positive, HER2 low-expressing population
timeFrame: Up to 25 months
measure: Duration of remission (DOR) as assessed by investigators in the HR-positive, HER2 low-expressing population
timeFrame: Up to 25 months
measure: Investigator-assessed clinical benefit rate (CBR) in the HR-positive, low HER2-expressing population
timeFrame: Up to 25 months
measure: Progression-free survival (PFS) as assessed by investigators in the HER2 low expression population
timeFrame: Up to 25 months
measure: Overall survival (OS) as assessed by investigators in the HER2 low expression population
timeFrame: Up to 25 months
measure: Duration of remission (DOR) as assessed by investigators in the HER2 low expression population
timeFrame: Up to 25 months
measure: Objective remission rate (ORR) as assessed by investigators in the HER2 low expression population
timeFrame: Up to 25 months
measure: Clinical benefit rate (CBR) as assessed by investigators in the HER2 low expression population
timeFrame: Up to 25 months
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and indicators of abnormal laboratory tests
timeFrame: Up to 52 months
measure: Blood concentrations of the ADC drug TQB2102, total antibodies, and the small molecule toxin TQ22723
timeFrame: Within 1 hour prior to the start of infusion for Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 7, and Cycle 12, and 0.5 to 2 hours after the end of infusion for Cycle 2, Cycle 3, Cycle 4, Cycle 7, and Cycle 12 (21 days as a treatment cycle).
measure: Immunogenicity of TQB2102: ADA incidence
timeFrame: Prior to (-60 min) the first day of dosing in Cycle 1, Cycle 2, Cycle 4, Cycle 7, and Cycle 12 (21 days as a treatment cycle), and at follow-up 30 days (±7 days) after the last dosing.
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical University
state: Anhui
city: Hefei
country: China
facility: AnHui Province Hospital West District
state: Anhui
city: Hefei
country: China
facility: The first Affiliated hospital of anhui medical university
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Quanzhou
country: China
facility: Fujian Medical University 2nd Affiliated Hospital
state: Fujian
city: Zhangzhou
country: China
facility: Zhangzhou Hospital in Fujian Province
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Hospital
state: Gansu
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Wuwei
country: China
facility: Gansu Wuwei Tumour Hospital
state: Gansu
city: Guangzhou
country: China
facility: Sun Yet-Sen University Cancer Certer
state: Guangdong
city: ZhanJiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Guigang
country: China
facility: Guigang City People'S Hospital
state: Guangxi
city: Nanning
country: China
facility: Cancer Hospital Affiliated to Guangxi Medical University
state: Guangxi
city: Nanning
country: China
facility: The First affiliated hospital of GuangXi medical university
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Cancer Hospital of Guizhou Medical University Co., LTD
state: Guizhou
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Haikou
country: China
facility: The First Affiliated Hospital of Hainan Medical College
state: Hainan
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Chengde
country: China
facility: Chengde Central Hospital
state: Hebei
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Anyang
country: China
facility: AnYang Tumor Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancar Hospital
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science & Technology
state: Hennan
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Chifeng
country: China
facility: Chifeng Municipal Hospital
state: Inner Mongolia
city: Dalian
country: China
facility: The Second Hospital of DALIAN Medical University
state: Liaoning
city: Binzhou
country: China
facility: Binzhou Medical College Affiliated Hospital
state: Shandong
city: Binzhou
country: China
facility: Binzhou People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Obstetrics & Gynecology Hospital of Fudan University
state: Shanghai
city: Baoji
country: China
facility: Baoji Central Hospital
state: Shanxi
city: Nanchong
country: China
facility: Affiliated Hospital of North Scichuan Medical College
state: Sichuan
city: Hangzhou
country: China
facility: Affiliated Hangzhou First People's Hospital
state: Zhejiang
Study officials:
References: