A Study of C-CAR039 (Prizloncabtagene Autoleucel) in Patients With Relapsed/Refractory Large B-Cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, single arm, open-label study. The purpose of the study is to evaluate safety of Prizloncabtagene Autoleucel (Prizlon-cel) and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of Prizlon-cel (Phase 2) in patients with relapsed or refractory large b-cell lymphoma (LBCL).

Detailed Description
-----------------
The purpose of the study is to evaluate the safety and efficacy of Prizlon-cel. It includes two phases, Phase 1b and Phase 2. In Phase 1b study, RP2D will be determined. The selected dose will be further evaluated in the Phase 2 study. The study includes the following sequential procedures: Screening, Apheresis and CAR-T manufacturing, Baseline, Lymphodepletion, CAR-T infusion, DLT period (Phase 1b) and Follow-up Visit. Subjects will be followed for at least 2 years after Prizlon-cel infusion, with up to 15 years long-term follow-up on a separate study.

Official Title
-----------------
A Phase 1b/2 Study of a Anti-CD19/CD20 Bispecific CAR-T Therapy (C-CAR039/Prizloncabtagene Autoleucel) in Patients With Relapsed/Refractory Large B-Cell Lymphoma

Conditions
-----------------
Relapsed/Refractory Large B-Cell Lymphoma

Intervention / Treatment
-----------------
* Biological: Prizloncabtagene autoleucel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years of age Histologically confirmed CD19 or CD20 positive B-cell non-Hodgkin lymphoma, including the following neoplasms as defined by the 2016 WHO classification of lymphoid neoplasms: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) Primary mediastinal large B-cell lymphoma (PMBCL) Transformed follicular lymphoma (tFL) High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) High-grade B-cell lymphoma, NOS (HGBL, NOS) Follicular lymphoma grade 3B (FL3B) Relapsed or refractory disease after ≥ 2 lines of standard therapy or relapsed after autologous stem cell transplantation (ASCT) At least one measurable lesion per the Lugano 2014 Classification Adequate organ and marrow function Exclusion Criteria: Prior allogeneic hematopoietic stem cell transplantation (HSCT) at anytime, or ASCT within 12 weeks prior to apheresis Suspected or confirmed central nervous system involvement Stroke or convulsion history within 6 months of signing informed consent form (ICF) Autoimmune disease, immunodeficiency or diseases requiring immunosuppressants treatment Uncontrolled active infection Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive hepatitis C virus (HCV) antibody with positive HCV RNA in peripheral blood; positive human immunodeficiency virus (HIV) antibody; positive syphilis test Severe heart, liver, renal or metabolism disease Inadequate wash-out time for previous anti-tumor treatments prior to apheresis Prior CAR-T therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prizloncabtagene Autoleucel<br>Prizlon-cel will be intravenously administered as a single infusion after lymphodepletion. | Biological: Prizloncabtagene autoleucel<br>* Prizlon-cel is a novel 2nd generation 4-1BB bispecific chimeric antigen receptor T-cell (CAR-T) targeting both CD19 and CD20 antigens<br>* Other names: C-CAR039;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Incidence and Severity of Adverse Events (AEs) | Incidence and severity of any AEs , including dose limiting toxicities (DLTs) | Up to 2 years after C-CAR039 infusion | 
| Phase 1b: Recommended Phase 2 Dose (R2PD) | Based on DLTs rates and overall safety profile | Up to 2 years after C-CAR039 infusion | 
| Phase 2: Overall Response Rate (ORR) at 3 months | Best response rate at 3 months after C-CAR039 infusion, including partial response (PR) and complete response (CR) | Up to 3 months after C-CAR039 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: ORR at 3 months | Best response rate at 3 months after C-CAR039 infusion, including PR and CR | Up to 3 months after C-CAR039 infusion | 
| Phase 2: Incidence and Severity of Adverse Events (AEs) | Incidence and severity of any AEs | Up to 2 years after C-CAR039 infusion | 
| ORR | Best response, including PR and CR | Up to 2 years after C-CAR039 infusion | 
| ORR at 6 months | Best response rate at 6 months after C-CAR039 infusion, including PR and CR | Up to 6 months after C-CAR039 infusion | 
| Duration of response (DOR) | The time from the first documented PR or CR to disease progression or death, whichever occurs first | Up to 2 years after C-CAR039 infusion | 
| Time to response (TTR) | The time from the date of C-CAR039 infusion to the first documented PR or CR | Up to 2 years after C-CAR039 infusion | 
| Progression-free survival (PFS) | The time from the date of C-CAR039 infusion to the date of first documented disease progression or death | Up to 2 years after C-CAR039 infusion | 
| Overall survival (OS) | The time from the date of C-CAR039 infusion to the date of death | Up to 2 years after C-CAR039 infusion | 
| Maximal plasma concentration (Cmax) | Maximal plasma concentration of C-CAR039 in peripheral blood | Up to 2 years after C-CAR039 infusion | 
| Time to reach the maximal plasma concentration (Tmax) | Time to reach the maximal plasma concentration of C-CAR039 in peripheral blood | Up to 2 years after C-CAR039 infusion | 
| Area under the curve within 28 days (AUC0-28d) | Area under the curve of C-CAR039 in peripheral blood within 28 days post infusion | Up to 28 days after C-CAR039 infusion | 
| Time of last measurable observed concentration (Tlast) | Time of last measurable observed concentration of C-CAR039 in peripheral blood | Up to 2 years after C-CAR039 infusion | 
| The B cell percentage changes and CD19/CD20 expression changes in blood | The B cell percentage changes and CD19/CD20 expression changes in blood by flow cytometry assay before and after C-CAR039 infusion | Up to 2 years after C-CAR039 infusion | 
| Anti-drug (C-CAR039) antibody | Presence of serum anti-drug (C-CAR039) antibody | Up to 2 years after C-CAR039 infusion |