Assessment of the Efficacy and Safety of Injectable TQB2934 (Subcutaneous Injection) in Systemic Light Chain Amyloidosis Patients

Официальное название

A Phase Ib/II Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of TQB2934 for Injection in Subjects With Systemic Light Chain Amyloidosis

Обзор

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.

Вмешательства

• Препарат TQB2934 injection
  TQB2934 for injection is a bispecific antibody targeting B-cell maturation antigen (BCMA) and Cluster of Differentiation 3 (CD3). One end binds to the CD3 receptor on the surface of T cells, while the other end binds to BCMA, recruiting T cells to BCMA-positive cells. This can activate T cells, which then release granzyme, perforin, and other enzymes to kill BCMA-positive malignant plasma cells, thereby reducing the level of monoclonal immunoglobulin light chains in the body and delaying further

Первичные конечные точки

• Numbers of subjects with adverse events (AEs), abnormal laboratory test values, and serious adverse events (SAEs) [Срок оценки: Baseline to the end of the study, about 4 years]
• The best hematological response evaluated by the Independent Review Committee (IRC) is complete remission (CR) [Срок оценки: Baseline to CR，about 1.5 years]

Вторичные конечные точки (12)

• Peak concentration (Cmax) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline to CR, about 1.5 years]
• Best overall hematologic response rate [Срок оценки: Baseline to CR/VGPR/PR, about 1.5 years]
• Minimal residual disease (MRD) negative rate [Срок оценки: Baseline to MRD negativity, about 1.5 years]
• Duration of hematologic response (DOR) [Срок оценки: The first date of PR/ VGPR/ CR to PD/ major organ failure /die, about 1.5 years]
• Duration of complete hematological remission (DOCR) [Срок оценки: The first date of CR to PD/ major organ failure /die, about 1.5 years]
• Cardiac relief rate [Срок оценки: Baseline to Cardiac relief, about 1.5 years]
• Renal remission rate [Срок оценки: Baseline to Renal remission, about 1.5 years]
• Liver response rate [Срок оценки: Baseline to liver remission, about 1.5 years]
• Main organ dysfunction progression-free survival (MOD-PFS) [Срок оценки: The first date of initial medication to PD/ major organ failure /die, about 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 27 центров

• Peking University First Hospital — Пекин
• Peking University People's Hospital — Пекин
• Southwest Hospital, Third Military Medical University (Army Medical University) — Чунцин
• Fujian Medical University Union Hospital — Фучжоу
• The First Affiliated Hospital, Sun Yat-sen University — Гуанчжоу
• Guangzhou First Municipal People's Hospital — Гуанчжоу
• Peking University ShenZhen Hospital — Шэньчжэнь
• The Affiliated Hospital of Guizhou Medical University — Guiyang
• … и ещё 19 центров

Идентификаторы

NCT: NCT07266116 · TQB2934-Ib/II-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗