IASO207 Injection in the Treatment of Relapsed/Refractory B-cell Malignancies

A Single-arm, Dose-escalation Clinical Study Evaluating the Safety, Pharmacokinetics and Preliminary Efficacy of IASO207 Injection in Subjects With Relapsed/Refractory B-cell Malignancies

This is a single-center, open-label, exploratory clinical study to evaluate the efficacy and safety of IASO207 Injection in patients with Relapsed/Refractory B-cell Malignancies。

Study Overview

• Status: Not yet recruiting
• Conditions: Malignancies
• Intervention / Treatment: Drug: IASO207 Injection

Detailed Description

This study is a single-arm, single-center, open-label First-in-Human clinical trial (FIH), aiming to preliminarily evaluate the safety and efficacy of IASO207 injection in patients with Relapsed/Refractory B-cell Malignancies,and to determine the recommended dose for subsequent clinical trials. The "3+3" dose-escalation design was adopted in the dose-escalation stage, and three dose-escalation dose groups of 5.0×10^8 TU, 1.0×10^9 TU and 2.0×10^9 TU were preset. Each dose group level included 3-6 subjects with a single dose. The objective is to preliminarily observe the safety and tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of IASO207 injection at different doses in patients with Relapsed/Refractory B-cell Malignancies and provide evidence for subsequent clinical trials.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age ≥ 18 years old and ≤ 75 years old.

• 2. Previously diagnosed by histopathological biopsy as one of the following pathological types:

  1. Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS); high-grade B-cell lymphoma (HGBL);
  2. DLBCL transformed from indolent lymphoma, including transformation from follicular lymphoma (FL) or marginal zone lymphoma (MZL), and DLBCL transformed from CLL/SLL (Richter transformation);
  3. Grade 3B follicular lymphoma (FL3B); primary mediastinal large B-cell lymphoma (PMBCL).

• 3. Recurrent/refractory B-cell lymphoma patients who have failed standard treatment (including recurrence, non-response, progression) must have received a standard immunotherapy regimen containing CD20 monoclonal antibody and anthracycline drugs:

  • Recurrent disease refers to the occurrence of disease recurrence or progression ≥ 12 months after treatment;
  • Refractory disease refers to disease progression during treatment or best response of disease stability (SD), or recurrence within 12 months after autologous hematopoietic stem cell transplantation, or disease progression within 12 months after treatment.

• 4. Before enrollment, it is confirmed that CD19 target expression is positive:

  1. Previous pathological results indicate positive CD19 expression, and/or;
  2. Can provide archived or fresh puncture specimens to the central laboratory for detection to confirm positive CD19 expression.
• 5. According to the Lugano 2014 standard, there is at least one measurable lesion (lymph node lesion LDi > 1.5 cm, extranodal lesion LDi > 1.0 cm);( LDi is longest diameter)
• 6. ECOG score 0-2;
• 7. Expected survival period ≥ 12 weeks;
• 8. Screening period examination confirms appropriate organ function: i. Blood routine: absolute neutrophil count (ANC) ≥ 1×109/L; platelets (PLT) ≥ 50×109/L; hemoglobin (Hb) ≥ 70g/L (must not have received any G-CSF/GM-CSF treatment or red blood cell and platelet transfusion within 7 days before laboratory examination); ii. Peripheral blood T lymphocyte absolute count ≥ 300 cells/μL; iii. Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5× upper limit of normal (ULN); serum total bilirubin ≤ 1.5× ULN (for patients with tumor liver metastasis: ALT/AST ≤ 5× ULN; TBil ≤ 3× ULN); iv. Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%; v. Pulmonary function: oxygen saturation at rest ≥ 91%; vi. Renal function: calculated creatinine clearance rate (CrCl) ≥ 40 ml/min according to Cockcroft-Gault formula; vii. Coagulation function: fibrinogen ≥ 1.0g/L; activated partial thromboplastin time (aPTT) ≤ 1.5× ULN, prothrombin time (PT) ≤ 1.5× ULN;
• 9. Pregnant participants should agree to take effective contraceptive measures or drugs from the date of signing the informed consent form until at least 1 year after the last administration of IASO207 injection.

Exclusion Criteria:

• 1. There is invasion of central nervous system tumors; and/or primary central nervous system DLBCL, primary testicular LBCL.
• 2. The tumor involves the small intestine, colon, and/or imaging examination indicates that the tumor involves the sub-mucosal layer of the gastrointestinal tract, and the patient has been evaluated to have a risk of organ perforation.
• 3. Within the past 5 years before screening, the subject has had other malignant tumors except for the disease under study, excluding cervical carcinoma in situ after radical treatment, basal cell or squamous cell skin cancer after radical treatment, local prostate cancer, breast duct carcinoma in situ or thyroid papillary carcinoma.
• 4. Infectious disease screening meets one of the following conditions: i. The subject has positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and abnormal peripheral blood HBV DNA test (abnormal HBV DNA test is defined as: HBV DNA quantitative test higher than the detection center's lower limit or higher than the normal reference range of the detection center or HBV DNA qualitative test positive); ii. The subject has positive hepatitis C virus (HCV) antibody and positive peripheral blood HCV RNA; iii. The subject has positive human immunodeficiency virus (HIV) antibody; iv. The subject has syphilis; v. The subject is an active CMV infection patient.
• 5. Before enrollment, there is uncontrollable active bacterial, fungal or viral infection: i. There are persistent symptoms/signs related to infection that require intravenous anti-infection drug treatment; ii. After appropriate anti-infection treatment, the clinical symptoms and examinations do not indicate improvement.
• 6. Severe heart disease: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months before screening), congestive heart failure (NYHA functional classification standard ≥ III), severe arrhythmia.
• 7. Within the past 6 months before screening, the subject has had central nervous system diseases or histories, such as epilepsy, paralysis, aphasia, cerebral infarction, cerebral hemorrhage, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome (such as cerebral aneurysm, epilepsy, stroke [except lacunar infarction], senile dementia, psychosis, etc.) or patients with consciousness disorders.
• 8. The subject has received any CD19-targeted treatment before.
• 9. The subject has received any allogeneic hematopoietic stem cell transplantation (Allo-HSCT), autologous CAR-T and other allogeneic donor cell adoptive therapy.
• 10. The subject with a large mass (diameter of the lesion > 7.5 cm) is not included in this study; patients whose disease progresses too rapidly and is expected not to benefit from the treatment of this study will not be included in this study.
• 11. Before enrollment, the subject does not meet the drug/treatment washout period: i. The subject needs or is continuously using systemic corticosteroids or other immunosuppressants within 4 weeks before enrollment; ii. The subject has received bispecific antibody, autologous hematopoietic stem cell transplantation, autologous CAR-T treatment within 12 weeks before enrollment; iii. The subject has received radiotherapy or grade 4 major surgery within 4 weeks before enrollment; or plans to undergo general anesthesia surgery within 12 weeks after receiving the study treatment.

iv. Using monoclonal antibodies, cytotoxic chemotherapy, or ADC drugs within 4 weeks prior to enrollment; v. Having received vaccination or any off-label clinical study drug treatment within 4 weeks prior to enrollment.

• 12. Judged by the investigator, there are other unstable systemic diseases: including but not limited to severe liver, kidney or metabolic diseases that require treatment.
• 13. The adverse reactions caused by previous anti-tumor treatment have not been alleviated to ≤ grade 2 (NCI-CTCAE v5.0 version).
• 14. Those with a history of allergic reactions to the excipient components of IASO207 injection.
• 15. Those who have received solid organ transplantation in the past.
• 16. Pregnant or lactating women.
• 17. Other situations deemed by the investigator as not suitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IASO207 Injection; IASO207 Injection will be infused at 5.0×10^8 TU or 1.0×10^9 TU or 2.0×10^9 TU after enrollment.

Drug: IASO207 Injection; IASO207 is a third-generation replication-deficient self-inactivating lentiviral vector that carries the gene encoding a second-generation anti-human CD19 chimeric antigen receptor (CD19 CAR) containing the 4-1BB co-stimulatory factor. IASO207 has been engineered through surface modification of the lentiviral envelope to enable it to selectively bind and transduce T cells within the body, thereby directly generating CD19 CAR-T cells in vivo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoint - Adverse Events (AEs)	Incidence and severity of adverse events as assessed by NCI-CTCAE v5.0 (except CRS and ICANS per 2019 ASTCT criteria).	up to 2 years from IASO207 Injection infusion
Safety endpoint - The incidence of dose-limiting toxicity (DLT)	Percentage of participants who experienced DLT within 28 days after IASO207 administration.	up to 28 days from IASO207 Injection infusion
Safety endpoint - The types,incidence and severity of abnormal laboratory tests	The types, incidence and severity of abnormal laboratory results assessed by CTCAEV5.0 will be analyzed and reported.	up to 2 years from IASO207 Injection infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy endpoint - Objective response rate (ORR)	ORR was defined as the percentage of participants who achieved partial response (PR) or better as assessed by the investigator according to the Lugano 2014 Criteria.	up to 2 years from IASO207 Injection infusion
Efficacy endpoint - Objective response rate (ORR) at pre-specified timepoints	ORR at 3, 6, 12 months as assessed by the investigator according to the Lugano 2014 Criteria.	up to 2 years from IASO207 Injection infusion
Efficacy endpoint - Complete response rate (CRR)	CRR was defined as the percentage of participants who achieved complete response (CR) as assessed by the investigator according to the Lugano 2014 Criteria.	up to 2 years from IASO207 Injection infusion
Efficacy endpoint - Duration of Response (DOR)	DOR was defined as the time (in months) from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death.	up to 2 years from IASO207 Injection infusion
Efficacy endpoint - Time to Response (TTR)	TTR was defined as the time between date of IASO207 administration and the first efficacy evaluation that the participant met all criteria for PR or better.	up to 2 years from IASO207 Injection infusion
Efficacy endpoint - Time to complete Response (TTCR)	Time from IASO207 Injection infusion to first documentation of complete response.	up to 2 years from IASO207 Injection infusion
Efficacy endpoint - Progression-free Survival (PFS)	PFS was defined as the time from the date of IASO207 administration to the date of first documented disease progression or death.	up to 2 years from IASO207 Injection infusion
Efficacy endpoint - Overall Survival (OS)	OS was defined as the time from the date of IASO207 administration to the date of the participant's death.	up to 2 years from IASO207 Injection infusion
Pharmacokinetic Endpoint - Cmax (viral particle)	Maximum concentration (Cmax) of viral particle titer in peripheral blood will be observed and calculated.	Up to 7 days from IASO207 Injection infusion
Pharmacokinetic Endpoint - Tmax (viral particle)	Peak time (Tmax) of viral particle titer in peripheral blood will be observed and analyzed.	Up to 7 days from IASO207 Injection infusion
Pharmacokinetic Endpoint - AUC0-7 (viral particle)	AUC0-7d refers to the area under the concentration-time curve from day 0 to day 7.	Up to 7 days from IASO207 Injection infusion
Pharmacokinetic Endpoint - Cmax (CAR-T cells)	The maximum concentration (Cmax) of CAR-T cells in peripheral blood after infusion.	up to 60 days from IASO207 Injection infusion
Pharmacokinetic Endpoint - Tmax (CAR-T cells)	The time for CAR-T cells to reach the maximum concentration (Tmax) after infusion.	up to 60 days from IASO207 Injection infusion
Pharmacokinetic Endpoint - AUC (CAR-T cells)	Area under the curve of 28 days and the last time point of PK measurement (AUC0-28d, AUC0-last) for CAR-T cells.	up to 60 days from IASO207 Injection infusion
Pharmacokinetic Endpoint - Cmax (VCN)	The maximum concentration (Cmax) of lentiviral vector copy number (VCN) in peripheral blood after infusion.	up to 2 years from IASO207 Injection infusion
Pharmacokinetic Endpoint - Tmax (VCN)	The time for VCN to reach the maximum concentration (Tmax) after infusion.	up to 2 years from IASO207 Injection infusion
Pharmacokinetic Endpoint - AUC (VCN)	Area under the curve of 28 days, 90 days, 180 days, and the last time point (AUC0-28d, AUC0-90d, AUC0-180d, AUC0-last) for VCN.	up to 2 years from IASO207 Injection infusion
Pharmacodynamic Endpoint - Changes in absolute count and percentage of B cells subsets in peripheral blood	To evaluate changes in the absolute count (cells/μL) and percentage of B cells in peripheral blood, measured by flow cytometry.	up to 2 years from IASO207 Injection infusion
Pharmacodynamic Endpoint - CRP	Changes in the levels of CRP.	up to 2 years from IASO207 Injection infusion
Pharmacodynamic Endpoint - Ferritin	Changes in the levels of Ferritin.	up to 2 years from IASO207 Injection infusion
Pharmacodynamic Endpoint - IL-6	Changes in the levels of IL-6.	up to 2 years from IASO207 Injection infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Prevalence and titer of confirmed human anti-CAR antibodies in peripheral blood.	up to 2 years from IASO207 Injection infusion
Replication competent lentivirus (RCL)	Prevalence of replication-competent lentivirus (RCL) in peripheral blood.	up to 2 years from IASO207 Injection infusion
Virus shedding	Presence of viral shedding in body fluid samples (urine, feces, and saliva).	Up to 7 days from IASO207 Injection infusion
percentage of CD19-positive target cells	Quantification of the percentage of CD19-positive target cells in baseline patient samples, measured by flow cytometry prior to IASO207 infusion.	Baseline (within 7 days before IASO207 infusion)
scRNA-seq	Based on single-cell RNA sequencing (scRNA-seq), to evaluate the dynamic changes of key cell subpopulation proportions, immune exhaustion-related gene expression profiles, and drug resistance signaling pathway activation levels from baseline to various post-treatment time points.	Up to 2 years from IASO207 Injection infusion
Baseline CD19 mean fluorescence intensity (MFI) on target cells	Quantification of CD19 mean fluorescence intensity (MFI) on target cells in baseline patient samples, measured by flow cytometry prior to IASO207 infusion.	Baseline (within 7 days before IASO207 infusion)

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2042

Study Registration Dates

• First Submitted: April 18, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; B-cell malignancies; IASO207
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Neoplasms; Recurrence
• Other Study ID Numbers: IASO207CI001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No