Epstein-Barr virus positive lymphomas
Conditions
Interventions
Intervention group 4:WGc-043 injection, 400ug
Intervention group 1:WGc-043 injection, 100ug
Intervention group 2:WGc-043 injection, 200ug
Intervention group 3:WGc-043 injection, 300ug
Sponsors
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine / West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.?? Participants aged >=18 years at screening, of either sex; ?2.?? Histologically or cytologically confirmed [per the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms (Revised 4th Edition, 2017)] relapsed/refractory Epstein-Barr virus (EBV)-positive lymphoma with failed standard therapy and lack of effective treatment options (?EBV positivity? must be confirmed by in situ hybridization (ISH or FISH) demonstrating EBER positivity in tumor tissue.), including but not limited to: NK/T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), or other peripheral T-cell lymphomas (PTCL), etc. ?Note:?? (1) Relapse is defined as the appearance of new lesions at the primary site or other sites after achieving complete remission (CR). (2) Refractory is defined as meeting any of the following criteria: failure to achieve partial remission (PR) after >=2 treatment cycles; failure to achieve CR after >=4 treatment cycles; failure to achieve CR after autologous hematopoietic stem cell transplantation (auto-HSCT); if the best response or treatment discontinuation reason is progressive disease (PD), the cycle number requirement is waived; (3) ?Prior therapy must include:?? 1) For relapsed/refractory DLBCL: At least two standard systemic treatment regimens; 2) For relapsed/refractory PTCL: At least one line of systemic therapy; 3) For NK/T-cell lymphoma: Must have received an asparaginase-based regimen [participants with stage I/II disease (per the Nasal-type NK/T-cell Lymphoma CA Staging System) must also have received radiotherapy]; 4) For relapsed/refractory HL: At least two lines of systemic therapy. ?3.?? Eastern Cooperative Oncology Group (ECOG) performance status score (see Appendix III, Section 16.3): 0–2; ?4.?? Estimated survival >=3 months; ?5.?? At least one evaluable or measurable lesion (per Lugano 2014 criteria): Measurable lesions are defined as: Lymph node lesions with a maximum diameter >15 mm (measured by contrast-enhanced CT, MRI, or PET-CT); Extranodal lesions with a maximum diameter >10 mm (measured by contrast-enhanced CT, MRI, or PET-CT). ?6.?? Adequate major organ function, with laboratory values meeting the following criteria: (1) Hemoglobin >=80 g/L; absolute neutrophil count (ANC) >1.0×10^9/L; platelet count >=75×10^9/L (no granulocyte colony-stimulating factor [G-CSF] or other hematopoietic stimulants within 14 days prior to laboratory testing; no blood transfusion within 7 days prior to testing); (2) Total bilirubin =50 mL/min (Cockcroft-Gault formula); (5) Prothrombin time (PT) and international normalized ratio (INR) =50%; (7) If any of the above parameters are below the protocol-defined lower limit due to lymphoma progression (as judged by the investigator), enrollment may be discussed with the sponsor and CRO medical team for final decision. ?7.?? No pregnancy planned during the trial period; willingness to use effective contraception during the trial and for 4 months after treatment discontinuation (applicable to subjects of childbearing potential); neg
Exclusion criteria
Exclusion criteria: 1.?? History of other malignancies, except for adequately treated and non-recurrent within 5 years prior to screening basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or gastrointestinal mucosal carcinoma, which the investigator deems eligible for inclusion; ?2.?? Known invasive NK-cell leukemia; central nervous system (CNS) lymphoma or CNS metastases; or hemophagocytic syndrome; ?3.?? Known clinically significant uncontrolled cardiac symptoms or diseases, such as: New York Heart Association (NYHA) Class II or higher heart failure (see Appendix IV, Section 16.4), unstable angina, myocardial infarction within the past 6 months, or clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; ?4.?? Any active autoimmune disease or history of autoimmune diseases, including but not limited to: neurologic diseases related to immunity, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disorders, scleroderma, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome (excluding type 1 diabetes mellitus controlled with stable-dose insulin); ?5.?? Any uncontrollable clinical disease (e.g., respiratory, circulatory, digestive, nervous, hematologic, genitourinary, or endocrine system diseases) or psychiatric disorders (e.g., depression, schizophrenia), or other major illnesses that, in the investigator's judgment, may impede the ability to provide informed consent or interfere with the interpretation of trial results or pose risks to the subject's participation or otherwise hinder the achievement of trial objectives; ?6.?? Known history of interstitial pneumonia or high suspicion of interstitial pneumonia; or pulmonary abnormalities that may interfere with the detection or management of suspected drug-related pulmonary toxicity during the trial; ?7.?? Hypersensitivity to the investigational drug (including any excipients); history of severe allergic reactions to any drug, food, or vaccine, including but not limited to: anaphylactic shock, anaphylactic laryngeal edema, anaphylactic dyspnea, allergic purpura, thrombocytopenic purpura, localized allergic necrotic reaction (Arthus reaction), etc.; ?8.?? Any abnormalities at the injection site or permanent body art (e.g., tattoos), which, in the investigator's judgment, may impede observation of local injection-site reactions; ?9.?? Contraindications to intramuscular injection (see Appendix V, Section 16.5); ?10.?? Systemic antineoplastic therapy (radiotherapy, chemotherapy, targeted therapy, immunotherapy, or local-regional treatment) within 4 weeks or 5 half-lives (whichever is shorter) prior to first dose, or palliative radiotherapy within 2 weeks prior to first dose; treatment-related adverse events (excluding alopecia) from prior antineoplastic therapy that have not resolved to NCI CTCAE Grade 10 mg/day prednisone or equivalent) or other immunosuppressants within 14 days prior to first dose (or 5 half-lives, whichever is shorter).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Type, frequency, and severity of DLT, treatment emergent adverse event (TEAE), and serious adverse event (SAE);MTD or RP2D;Significant abnormalities in other safety assessments, including physical examinations, vital signs, and 12-lead electrocardiograms (12-ECG); | — |
Secondary
| Measure | Time frame |
|---|---|
| Types, frequencies, and severity of abnormal laboratory test results (NCI CTCAE v5.0);Objective response rate (ORR);Disease control rate (DCR);Duration of response (DoR);Progression-free survival (PFS);Overall survival (OS);Pharmacokinetic (PK) characteristics;Immunogenicity (Example: Antigen-specific T-cell levels in peripheral blood mononuclear cells [PBMCs]; immune cell subsets; anti-PEG antibody titers);Efficacy-related biomarkers (Example: Levels of EBV DNA copies in peripheral blood and programmed death-ligand 1 [PD-L1] expression in tumor tissue); | — |
Countries
China
Contacts
Public ContactWeili Zhao/Ting Niu
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine/West China Hospital, Sichuan University
Outcome results
None listed