Overview

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.

Eligibility

Inclusion Criteria:

• The subjects voluntarily joined this study, signed the informed consent form, and exhibited good compliance;
• Aged 18 to 75 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 have experienced disease recurrence or progression after the last line of treatment was ineffective or the duration of response to the last line of treatment was less than 12 months;
• 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.

Exclusion Criteria:

• Diagnosed with other types of amyloidosis, active plasma cell leukemia, 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;
• 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;
• Have had asthma within 2 years before the first medication or currently suffer from asthma;
• Individuals with significant cardiovascular diseases;
• Individuals with a history of immune deficiency, or active autoimmune diseases requiring systemic immunosuppressive therapy, etc
• Subjects deemed unsuitable for enrollment by the researchers.