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 Phase I:To observe and evaluate the safety and tolerability of IMV101 in subjects with relapsed/refractory B-cell non-Hodgkin lymphoma.
Phase IIa:To determine the Recommended Phase II Dose (RP2D) based on integrated safety and efficacy data following IMV101 treatment.
To evaluate the preliminary antitumor efficacy of IMV101. Secondary Study Objectives:To evaluate other safety parameters following IMV101 treatment.
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles following administration of IMV101.
Exploratory Objective:To 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).
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.
Pregnant or lactating women.
Subjects with active central nervous system (CNS) involvement or intestinal parenchymal involvement by B-cell non-Hodgkin lymphoma.
Presence of lymphoma cells in cerebrospinal fluid (CSF), brain metastases, or a history of CNS lymphoma, primary CNS lymphoma, or previously detected lymphoma cells in CSF or brain metastases.
Subjects with lymphoma infiltration of the atria or ventricles.
Sequential
IMV101 treatment
DrugIMV101 Dose Escalation Scheme: Dose Level DL-1，Dose 1e7、Dose Level DL1，Dose 3e7、Dose Level DL2 Dose 1e8、Dose Level DL3 Dose 3e8、Dose Level DL4 Dose 1e9；Accelerated Titration: The 3×10⁷ TU/subject dose cohort will enroll one subject. If this subject experiences a Grade ≥2 adverse event related to IMV101, the cohort will transition to the standard "3+3" design by enrolling two additional subjects for safety and tolerability assessment.
DLTs/RP2D/Efficacy endpoint
To observe the incidence of dose-limiting toxicities (DLTs) within 28 days following IMV101 administration.To determine the Recommended Phase II Dose (RP2D) of IMV101.Efficacy endpoints: Time to response (TTR), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Objective response rate includes stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR), assessed according to the Lugano 2014 classification for lymphoma efficacy assessment (Cheson, 2014).
Treatment-related adverse events (TRAEs)
Assessment of the incidence and severity of treatment-related adverse events (TRAEs) will be conducted according to the NCI CTCAE version 5.0, with the exception of CRS and ICANS, which will be graded per the 2019 ASTCT consensus criteria.
Assessment of pharmacokinetic (about Cmax)
The maximum concentration of CAR-T cells in peripheral blood after administration (Cmax)
Assessment of pharmacokinetic (about Tmax)
The time to reach the maximum concentration (Tmax)
Assessment of pharmacokinetic (about AUC0-28d)
The area under the CAR-T concentration versus time curve (AUC) for 28 days after IMV101 administration
To evaluate the immunogenicity of IMV101 injection
The positive rate of human anti-CAR antibody at each time point
RCL testing
To detect the presence of replication-competent lentivirus (RCL) in peripheral blood.
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