Clinical Study of Recombinant Anti-CD19m-CD3 Antibody Injection (A-319)

Recombinant Anti-CD19m-CD3 Antibody Injection (A-319) for Refractory/Relapsed or MRD-Positive After Induction Chemotherapy Acute B-Cell Lymphoblastic Leukemia (B-ALL) Clinical Study

This is an exploratory study with an open-label, single-arm, single-center design. It plans to enroll subjects with refractory/relapsed acute B-cell lymphoblastic leukemia (B-ALL), or treatment-naive or previously treated B-ALL subjects who achieved complete remission (CR) after induction chemotherapy but still have positive minimal residual disease (MRD). The primary objectives are to preliminarily evaluate the safety, tolerability, pharmacokinetics, biology, preliminary efficacy, and immunogenicity of A-319 subcutaneous injection.

Inclusion Criteria:

All of the following criteria must be met for refractory/relapsed acute B-cell lymphoblastic leukemia:

• 1.Aged 18 to 75 years (inclusive), regardless of gender;
• 2.Confirmed diagnosis of refractory or relapsed acute B-cell lymphoblastic leukemia (B-ALL) with positive CD19 expression. Definition of refractory or relapsed: failure to respond to conventional induction chemotherapy; early relapse (relapse within 12 months of first remission); relapse after 12 months of first remission with failure to achieve remission following re-induction with the original regimen; second or subsequent relapse, relapse after autologous hematopoietic stem cell transplantation (Auto-HSCT), or relapse after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). (For patients with Philadelphia chromosome-positive [Ph+] disease, they must have received treatment with at least one tyrosine kinase inhibitor [TKI].);
• 3.Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;
• 4.Bone marrow blast percentage of at least 5% (determined by morphology);
• 5.Expected life expectancy of at least 3 months;
• 6.Ability to sign the informed consent form and comply with protocol requirements; if the patient is unable to sign, their legal guardian or representative must sign on their behalf.

All of the following criteria must be met for acute B-cell lymphoblastic leukemia (B-ALL) with positive minimal residual disease (MRD) despite achieving complete remission (CR) via induction chemotherapy:

• 1.Aged 18 to 75 years (inclusive), regardless of gender;
• 2.Confirmed diagnosis of acute B-cell lymphoblastic leukemia (B-ALL) with positive CD19 expression;
• 3.B-ALL that has achieved complete morphological remission (CR) via at least 2 cycles of induction chemotherapy# but remains minimal residual disease (MRD)-positive. MRD positivity is defined as detectable nucleated blast cells ≥ 10-⁴. (For patients with Philadelphia chromosome-positive [Ph+] disease, they must have received treatment with tyrosine kinase inhibitors [TKIs] combined with chemotherapy);
• 4.Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;
• 5.Ability to sign the informed consent form and comply with protocol requirements; if the patient is unable to sign, their legal guardian or representative must sign on their behalf.

Exclusion Criteria:

• 1.Central nervous system (CNS) leukemia (confirmed by cerebrospinal fluid [CSF] analysis) or acute lymphoblastic leukemia (ALL) with clinically relevant CNS involvement;
• 2.Burkitt's leukemia, testicular infiltration in acute lymphoblastic leukemia (ALL);
• 3.A history of malignancy other than ALL within 5 years prior to the initiation of protocol-specific treatment. Exceptions include: malignancies treated with curative intent, with no known active disease for 5 years before enrollment, and deemed by the treating physician to have a low recurrence risk; non-melanoma skin cancer or lentigo maligna that has been adequately treated with no evidence of recurrence; carcinoma in situ of the cervix that has been adequately treated with no evidence of recurrence; ductal carcinoma in situ of the breast that has been adequately treated with no evidence of recurrence;and prostatic intraepithelial neoplasia with no evidence of prostate cancer;
• 4.Patients with grade 2-4 acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), or those with chronic GVHD requiring immunosuppressive therapy;
• 5.Receipt of autologous hematopoietic stem cell transplantation (Auto-HSCT) within 6 weeks, or allogeneic hematopoietic stem cell transplantation (Allo-HSCT) within 3 months, prior to the start of study drug treatment;
• 6.Concurrent chemotherapy, radiotherapy, or systemic treatment for GVHD within 2 weeks prior to the start of study drug treatment;
• 7.Patients with diseases, medical conditions, or social factors that, in the investigator's judgment, may affect study results or compliance. The protocol specifies the following conditions that disqualify patients from participating in the study: uncontrolled acute infection or confirmed bacteremia; known human immunodeficiency virus (HIV) infection, or acute hepatitis B or hepatitis C; patients with severe dyspnea, impaired pulmonary function, or requiring continuous oxygen supplementation; New York Heart Association (NYHA) heart failure classification of grade 3 or 4; myocardial infarction, unstable angina, stroke, transient ischemic attack, severe arrhythmia, or uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) within 6 months prior to drug administration;
• 8.Laboratory test requirements are as follows: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN), or > 5 × ULN if liver metastasis is present; total bilirubin > 1.5 × ULN;creatinine clearance < 50 mL/min (calculated using the Cockroft-Gault formula); coagulation function: International Normalized Ratio (INR) > 1.6 (unless on anticoagulant therapy);for patients on oral anticoagulant therapy with a stable dose (for at least 14 days) (e.g., warfarin), INR must be ≤ 3.0 with no bleeding tendency (i.e., no bleeding within 14 days prior to the first dose of the study drug); use of low-molecular-weight heparin is permitted for subjects;
• 9.Previous receipt of anti-CD19 therapy (including CAR-T cell therapy), or immunotherapy (e.g., rituximab) within 4 weeks prior to A-319 treatment;
• 10:Presence of adverse events (except alopecia) caused by anti-tumor treatment that have not resolved to grade 1;
• 11.Pregnant women (positive pregnancy test), lactating women, or women of childbearing potential who refuse to use contraception from the time of signing the informed consent form until at least 3 months after the end of the study; women of childbearing potential must have a positive pregnancy test (human chorionic gonadotropin [HCG] test) within 7 days prior to Day 1 of treatment;
• 12.Male patients (except those who have undergone surgical sterilization) who refuse to use contraception from the time of signing the informed consent form until at least 3 months after the end of the study;
• 13.Known hypersensitivity to the study drug or its excipients;
• 14.Patients deemed unsuitable for participation in this study by the investigator.