Clinical trial NCT06854445: Clinical Trial of TQB2825 Injection Combined With Chemotherapy in Subjects With Diffuse Large B-cell Lymphoma
Official title: Phase II Clinical Trial of TQB2825 Injection Combined With Chemotherapy in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large Cell B-lymphoma
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-03-03
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the preliminary efficacy of TQB2825 in combination with chemotherapy in subjects with diffuse large B-cell lymphoma.


Eligibility criteria: Inclusion Criteria:

* The subjects voluntarily participate in this study, sign the informed consent form, and have good compliance;
* Age ≥18 years (calculated from the date of informed consent);
* Eastern Cooperative Oncology Group (ECOG) score 0 \~ 2 points;
* Expected survival greater than 12 weeks;
* Histological or cytological diagnosis of diffuse large B-cell lymphoma in accordance with the World Health Organization (WHO) diagnostic criteria in 2022;
* Pathological diagnosis results containing CD20 positive expression and Myc rearrangement negative after anti-CD20 treatment must be provided;
* Subjects with relapsed or refractory diffuse large B-cell lymphoma who have received at least 1 line of systemic therapy;
* Not suitable for hematopoietic stem cell transplantation;
* According to the Lugano criteria in 2014, there is at least one measurable lesion, that is, the long diameter of lymph node lesions \> 15 mm or extranodal lesions \> 10 mm according to CT cross-sectional images; Positron emission tomography - computerized tomography (PET-CT) scan shows PET positive;
* Laboratory tests meet specific criteria;
* Adopt effective contraceptive measures;

Exclusion Criteria:

* Subjects who had or currently had other malignant tumors within 5 years prior to the first dose;
* Previous or current involvement or suspected involvement of the central nervous system by lymphoma;
* Failure to recover from adverse reactions to Common Terminology Criteria for Adverse Events version 5.0 (CTCAEv5.0) criteria ≤ grade 1 from previous treatment;
* History of previous anti-tumor treatment:

  1. previous use of other antibody drugs targeting CD3 and CD20 at the same time;
  2. received Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) therapy, or other immune cell therapy, or autologous hematopoietic stem cell transplantation (auto-HSCT) within 3 months before the first dose;
  3. previous treatment with R-GemOx or GemOx;
  4. received chemotherapy, immunotherapy, monoclonal antibody therapy 4 times before the first dose, 2 times received radiotherapy or small molecule targeted drugs, or subjects who are still within 5 half-lives of the drug, the washout period is calculated from the end time of treatment;
  5. received treatment with Chinese patent medicines with clear anti-tumor indications in the package insert of National Medical Products Administration (NMPA)-approved drugs 2 times before the first dose;
* Subjects who have undergone major surgical treatment, significant traumatic injury, or expected major surgery during the study treatment period within 4 weeks prior to the first use of medication, or have long-term untreated wounds or fractures;
* Subjects who experience any bleeding or bleeding events ≥ Common Terminology Criteria Adverse Event (CTC AE) grade 3 within 4 weeks prior to the first administration;
* Hyperactive/venous thrombotic events within 6 months prior to first dose,Such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism or any other history of severe thromboembolism;
* Clinically significant uncontrolled pleural effusion, ascites and more than moderate pericardial effusion requiring repeated drainage;
* Decompensated cirrhosis (Child-Pugh class B or C liver function) and active hepatitis;
* Pulmonary disease, including any of the following: 1) with or without current pneumonitis requiring corticosteroid therapy; 2) with or suspected chronic obstructive pulmonary disease (COPD), and forced expiratory volume in 1 second (FEV1) \< 60% (predicted);
* Brain or mental disorders;
* Have major cardiovascular disease;
* Active or uncontrolled infection (≥ CTCAE grade 2 infection), including bacterial, fungal or viral infections including but not limited to active pneumonia, syphilis and tuberculosis.
* Unexplained fever \> 38.5℃ during screening or before the first dose;
* Renal failure requiring hemodialysis or peritoneal dialysis, previous history of nephrotic syndrome;
* History of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency diseases;
* Have or have had prior autoimmune disease requiring treatment.
* Prepare to undergo or have previously received organ transplantation, or have a significant host transplant response, or have previously received allogeneic hematopoietic stem cell transplantation; 19、Need to receive systemic immunosuppressive therapy;
* Known or suspected history of hemophagocytic syndrome (HLH);
* Known hypersensitivity to excipient components of the study drug.
* Subjects who participated in other anti-tumor clinical trials within 4 or 5 half-lives before the first dose.
* Any condition that, in the judgment of the investigator, would jeopardize the safety of the subject or prevent the subject from completing the study.

Primary outcomes:
measure: Complete response rate (CR rate)
timeFrame: 1 year
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 1 year
measure: Progression-free survival (PFS)
timeFrame: 1 year
measure: Duration of Response (DOR)
timeFrame: 1 year
measure: Time to Response (TTR)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 3 years
measure: Half-life (t1/2)
timeFrame: Pre-dose, 5 minutes, 24, 72, 120 and 168 hours post dose on day 1 of cycles 2, 4; pre-dose, 5 minutes post dose on day 1 of cycles 3, 8; once at the end of treatment, each cycle is 21 days
measure: Area under the plasma concentration-time curve (AUC0-last)
timeFrame: Pre-dose, 5 minutes, 24, 72, 120 and 168 hours post dose on day 1 of cycles 2, 4; pre-dose, 5 minutes post dose on day 1 of cycles 3, 8; once at the end of treatment, each cycle is 21 days
measure: Apparent clearance (CL)
timeFrame: Pre-dose, 5 minutes, 24, 72, 120 and 168 hours post dose on day 1 of cycles 2, 4; pre-dose, 5 minutes post dose on day 1 of cycles 3, 8; once at the end of treatment, each cycle is 21 days
measure: Apparent volume of distribution at terminal phase (Vz)
timeFrame: Pre-dose, 5 minutes, 24, 72, 120 and 168 hours post dose on day 1 of cycles 2, 4; pre-dose, 5 minutes post dose on day 1 of cycles 3, 8; once at the end of treatment, each cycle is 21 days
measure: Trough plasma concentration (Cmin)
timeFrame: Pre-dose, 5 minutes, 24, 72, 120 and 168 hours post dose on day 1 of cycles 2, 4; pre-dose, 5 minutes post dose on day 1 of cycles 3, 8; once at the end of treatment, each cycle is 21 days
measure: Anti-drug antibody (ADA ) incidence
timeFrame: 2 years
Other outcomes:
Locations:
city: Wuhu
country: China
facility: The First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital and insititute Guangzhou Medical University
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital (HBCH)
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Dalian
country: China
facility: The Second Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Shandong cancer hospital
state: Shandong
city: Weihai
country: China
facility: Weihai Central Hospital
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincal People's Hospital
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Hangzhou
country: China
facility: THE First Affiliated Hospital ZheJiang University School of Medicine
state: Zhejiang
Study officials:
References: