A Phase I/IIa, Open-label, Single-center, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of IMV101 as a Single Agent in Subjects With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Objectives: o evaluate other safety parameters following IMV101 treatment. To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles following administration of IMV101. Exploratory
Objective: o evaluate biomarkers change pre- and post-IMV101 administration and their correlation with efficacy and safety. To perform long-term follow-up for immunogenicity analysis, viral shedding studies, tumor multi-omics research, lentiviral integration sites, and replication-competent lentivirus (RCL), among others.
• Aged 18 years or older, any sex.
• Previously histologically or cytologically confirmed relapsed/refractory B-cell non-Hodgkin's lymphoma, including the following WHO-defined types: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL), and mantle cell lymphoma (MCL), among others.
• CD19 positivity confirmed by pathology or flow cytometry analysis (subjects with prior exposure to CD19-targeted therapies must undergo repeat biopsy prior to enrollment to reconfirm CD19-positive status).
• Relapsed/refractory B-cell non-Hodgkin lymphoma meeting at least one of the following criteria:
‣ Disease progression after at least two prior lines of systemic therapy (including relapse, treatment failure, or disease progression), with documented prior exposure to both an anti-CD20 monoclonal antibody (unless CD20-negative) and an anthracycline-based chemotherapy regimen.
⁃ Relapsed disease following autologous hematopoietic stem cell transplantation; or relapse occurring ≥2 years after allogeneic hematopoietic stem cell transplantation, in the absence of ongoing immunosuppressive therapy.
⁃ Primary refractory disease, defined as stable disease or disease progression as best response after at least two cycles of initial anti-CD20-based immunochemotherapy.
‣ 5． According to the Lugano lymphoma response criteria (Cheson et al, 2014), at least one measurable lesion must be present, meeting one of the following conditions:
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‣ A nodal lesion with a long axis \>15 mm (short axis may be used if measurable).
⁃ An extranodal lesion with both long and short axes \>10 mm. Lesions previously irradiated will only be considered measurable if documented progression has occurred after radiation therapy.
‣ 6． Life expectancy ≥ 12 weeks. 7． ECOG performance status score of 0 or 1. 8． Subjects must have adequate organ and marrow function. Laboratory screening must meet all of the following criteria, with all values falling within the specified ranges without ongoing supportive care. If any laboratory result is outside these limits, one repeat test is permitted within one week. If the repeat result still does not meet the criteria, the subject fails screening and is ineligible for enrollment:
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‣ Hematological criteria (in the absence of intensive transfusion \[≥2 times within 1 week\], platelet administration, or growth factor support \[with the exception of recombinant erythropoietin\] within 7 days prior to testing).
⁃ Hepatic Function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤2.5×ULN, and total bilirubin ≤2×ULN (except in subjects with Gilbert's syndrome); for those with documented hepatic involvement by lymphoma, ALT and AST must be \<5×ULN.
⁃ Renal Function: Serum creatinine ≤1.5×ULN; if serum creatinine exceeds this threshold, creatinine clearance must be \>50 mL/min (calculated using the Cockcroft-Gault formula). Urine protein dipstick must be ≤1+; if dipstick result is ≥2+, 24-hour urine protein quantification is required (acceptable if \<1 g/24h).
‣ 9． All toxicities from prior anticancer therapy must have resolved to Grade 0-1 (per NCI CTCAE v5.0) or to a level meeting the study's inclusion/exclusion criteria. Exceptions include alopecia, vitiligo, and other toxicities considered by the investigator to pose no safety risk to the subject.
‣ 10．Reproductive Status: Females of childbearing potential or male subjects with female partners of childbearing potential must be willing to use highly effective medically approved contraception from the time of informed consent until 12 months after IMV101 administration. Acceptable methods include intrauterine devices or condoms (childbearing potential includes premenopausal women and women within 24 months of menopause).
‣ 11． Subjects must provide signed and dated written informed consent. 12．Subjects must demonstrate willingness and ability to comply with the prescribed treatment plan, laboratory tests, follow-up visits, and other study requirements.