A Phase Ib/II Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of TQB2934 for Injection in Subjects With Systemic Light Chain Amyloidosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 70
- 试验地点
- 25
- 主要终点
- Numbers of subjects with adverse events (AEs), abnormal laboratory test values, and serious adverse events (SAEs)
研究概览
简要总结
This study is a clinical trial aimed at the marketing of TQB2934 for injection. The project plans to enroll 70 subjects, including 13-21 subjects in Phase Ib, to evaluate the safety and preliminary efficacy, pharmacokinetic (PK) characteristics, immunogenicity, and pharmacodynamic (PD) of TQB2934 for injection in subjects with systemic light chain amyloidosis, and to determine the recommended Phase II dose (RP2D). The Phase II plan involves enrolling 49 subjects, aiming to demonstrate that in adult subjects with relapsed/refractory systemic light chain amyloidosis who have previously received treatment with daratumumab and bortezomib, TQB2934 for injection significantly improves the hematological complete response (CR) rate compared to historical controls. The primary endpoint is the optimal hematological CR rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subjects voluntarily joined this study, signed the informed consent form, and exhibited good compliance;
- •Aged 18 to 80 years old, with an Eastern Cooperative Oncology Group (ECOG) score of 0 to 2, and an expected survival of more than 12 weeks;
- •Systemic light chain amyloidosis with diagnostic records (i.e., primary light chain amyloidosis);
- •Presence of measurable lesions;
- •At least one organ involved;
- •Have previously received at least one line of systemic treatment, and recurred and progressed after the remission of the last line treatment;
- •N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≤ 8500 ng/L;
- •The corresponding organ function conforms to the protocol requirements;
- •Women of childbearing age should agree to use contraception during the study period and for 6 months after its completion; they must have a negative serum pregnancy test within 7 days before enrollment in the study and must be non-lactating subjects; men should agree to use contraception during the study period and for 6 months after its completion.
排除标准
- •Diagnosed with other types of amyloidosis, active plasma cell leukemia, active multiple myeloma, etc.
- •Have received allogeneic hematopoietic stem cell transplantation within 1 year prior to the first dose, or have received autologous hematopoietic stem cell transplantation within 12 weeks prior to the first dose;
- •Previously received treatment with drugs targeting the same target;
- •Within 4 weeks prior to the first dose, the patient has received a cumulative dose of dexamethasone >160 mg or an equivalent dose of other glucocorticoids, or within 3 weeks prior to the first dose, the patient has received targeted therapy, cytotoxic drugs, or any antibody therapy, or within 2 weeks prior to the first dose, the patient has received proteasome inhibitor therapy or radiotherapy, or within 1 week prior to the first dose, the patient has received immunomodulator therapy;
- •Those who have received treatment with traditional Chinese patent medicines and simple preparations with clear anti-tumor indications specified in the National Medical Products Administration (NMPA) approved drug instructions within 2 weeks before the first administration;
- •Those who have received attenuated live vaccine within 4 weeks before the first dose or plan to receive attenuated live vaccine during the study period;
- •Individuals with a history of severe allergies of unknown cause, or known allergies to monoclonal antibody drugs or exogenous human immunoglobulins, or known allergies to the excipients in injectable TQB2934 or pharmaceutical preparations;
- •Having had or currently suffering from other malignant tumors within 3 years before the first medication;
- •Unresolved toxic reactions above Common Terminology Criteria (CTC) AE Grade 1 caused by any previous treatment;
- •Those who have undergone major surgical treatment, significant traumatic injury, or are expected to undergo major surgery during the study treatment period within 4 weeks before the first dose of medication;
- •Arterial/venous thromboembolic events occurred within 6 months before the first dose;
- •Individuals with a history of abuse of psychotropic drugs who are unable to quit or who have mental disorders; or intractable seizures that require treatment;
- •Those with unsatisfactory blood pressure control;
- •Patients with poorly controlled diabetes;
- •Patients who have active or uncontrolled severe bacterial, viral, or systemic fungal infections (≥CTC AE Grade 2 infections) within 4 weeks before the first dose of medication;
- •Patients with hepatitis or decompensated liver cirrhosis (Child-Pugh Class B or C);
- •Individuals with active tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonia requiring treatment, or clinically symptomatic active pneumonia;
- •Those who have experienced asthma within 2 years before the first medication or currently suffer from asthma or chronic obstructive pulmonary disease;
- •Individuals with significant cardiovascular diseases;
- •Individuals with a history of immune deficiency, or active autoimmune diseases requiring systemic immunosuppressive therapy, etc.
- •Exclude subjects with organ failure unrelated to systemic light-chain (AL) amyloidosis;
- •Subjects deemed unsuitable for enrollment by the researchers.
研究组 & 干预措施
TQB2934 injection
TQB2934 injection 40 mg and 60 mg During cycles 1-3, medication is administered once a week. From the end of cycles 4-6, medication is administered once every two weeks. For patients who have not achieved complete remission (CR) or have MRD positivity after six cycles of medication, medication is administered once every eight weeks, with a maximum treatment duration of no more than two years
干预措施: TQB2934 injection (Drug)
结局指标
主要结局
Numbers of subjects with adverse events (AEs), abnormal laboratory test values, and serious adverse events (SAEs)
时间窗: Baseline to the end of the study, about 4 years
The occurrence of all adverse events (AEs), serious adverse events (SAEs), incidence and severity of adverse events (AEs), abnormal laboratory test values, and serious adverse events (SAEs).
The best hematological response evaluated by the Independent Review Committee (IRC) is complete remission (CR)
时间窗: Baseline to CR，about 1.5 years
Percentage of subjects who achieved complete hematological remission (CR) after receiving TQB2934 for injection among adult subjects with relapsed/refractory systemic light chain amyloidosis who had previously received treatment with duramycin and bortezomib.
次要结局
- Peak concentration (Cmax)(Pre-dose Cycle 1 day 1/day 8, post dose Cycle 1 day 8/Cycle 3 day 1 2, 6, 24, 48, 72, 120 hours; pre-dose cycle 1 day 15, 22,cycle 2 day 1, cycle 4 day 1, cycle 6 day 1, cycle 12 day 1 and EOT)
- Immunogenicity incidence rate and its changes over time(pre-dose day 8, cycle 2 day 1, cycle 6 day 1, cycle 12 day 1 and End of Treatment (EOT))
- Exploring the correlation between soluble BCMA in peripheral blood and the efficacy of TQB2934(pre-dose cycle 1 day 1, day 8, cycle 2 day 1, cycle 3 day 1, cycle 6 day 1, cycle 12 day 1; post dose cycle 1 day 1/day 8/cycle 3 day 1 6 hours; 56 days after the last administration)
- The best hematologic complete remission rate evaluated by researchers(Baseline to CR, about 1.5 years)
- Best overall hematologic response rate(Baseline to CR/VGPR/PR, about 1.5 years)
- Minimal residual disease (MRD) negative rate(Baseline to MRD negativity, about 1.5 years)
- Duration of hematologic response (DOR)(The first date of PR/ VGPR/ CR to PD/ major organ failure /die, about 1.5 years)
- Duration of complete hematological remission (DOCR)(The first date of CR to PD/ major organ failure /die, about 1.5 years)
- Cardiac relief rate(Baseline to Cardiac relief, about 1.5 years)
- Renal remission rate(Baseline to Renal remission, about 1.5 years)
- Liver response rate(Baseline to liver remission, about 1.5 years)
- Main organ dysfunction progression-free survival (MOD-PFS)(The first date of initial medication to PD/ major organ failure /die, about 2 years)
- Overall survival (OS)(The first date of initial medication to die, about 2 years)
- Major Organ Dysfunction-Event-Free Survival (MOD-EFS)(The first date of initial medication to PD/ major organ failure /die, about 2 years)