Targeting CD19/CD20 Dual-targeted Cell in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LUCAR-G39P, a Dual-targeted Cell Preparation Targeting CD19/CD20, in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LUCAR-G39P, a dual-targeted cell preparation targeting CD19/CD20, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma

Study Overview

• Status: Recruiting
• Conditions: Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Biological: LUCAR-G39P cells product

Detailed Description

his is an open-label, dose-escalation/dose extension study to assess the safety, tolerability, and efficacy of LUCAR-G39P in the patient ≥ 18 years of age with relapsed or refractory B-cell non-Hodgkin lymphoma. Subjects who meet the eligibility criteria will receive a single dose of LUCAR-G39P injection. The study will include the following sequential phases: screening, pre-treatment (lymphodepleting chemotherapy), treatment, and follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Huayuan Zhu, PhD,MD; Phone Number: +86-13813810650; Email: huayuan.zhu@hotmail.com

Study Locations

• China
  • Jiangsu
    • Nanjin, Jiangsu, China, 210029
      • Recruiting
      • Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital
      • Contact: Huayuan Zhu, PhD，MD; Phone Number: 86 25 68306034; Email: huayuan.zhu@hotmail.com
      • Contact: Yeqin Sha, MD; Email: yeqinsha@njmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent.
2. Aged 18-75 years (inclusive).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Histologically confirmed B-cell non-Hodgkin Lymphoma that expresses at least one of CD19/CD20.
5. At least one evaluable tumor lesion according to Lugano 2014 criteria.

Response to prior therapy is consistent with one of the following:

1. Primary refractory.
2. Relapsed or refractory after 2 or more lines of therapy.

3. For LBCL, 3B FL. t-iNHL:

   • Relapse within 12 months after first-line chemoimmunotherapy to achieve CR;

   • Progression or relapse within 12 months after autologous hematopoietic stem cell transplantation;

     7. Life expectancy≥ 3 months 8. Clinical laboratory values meet screening visit criteria

   Exclusion Criteria:

   Subject eligible for this study must not meet any of the following criteria:

   1. Prior antitumor therapy with insufficient washout period ;
   2. Patients who received autologous CAR-T cell therapy (except CD19-targeted) or autologous gene therapy;
   3. Patients who received allogeneic hematopoietic stem cell transplantation or allogeneic therapy;

   5. Patients who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus antibody (HIV- Ab).

   6. Known life-threatening allergies, hypersensitivity, or intolerance to LUCAR-G39P CAR-T cell or its excipients, including DMSO.

   7. Pregnant or lactating women;

   -

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: Experimental: LUCAR-G39P cells product; Each subject will be given a single-dose LUCAR-G39P cells infusion at each dose level.	Biological: LUCAR-G39P cells product; LUCAR-G39P cells product Prior to infusion of the LUCAR-G39P, subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and type of TEAEs	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Through study completion , an average of 2 years after LUCAR-G39P infusion (Day 1)
Pharmacokinetics in peripheral blood	CAR positive T cells and CAR transgene levels in peripheral blood after LUCAR-G39P infusion	ThTrough study completion , an average of 2 years after LUCAR-G39P infusion (Day 1)
Pharmacokinetics in bone marrow	CAR positive T cells and CAR transgene levels in bone marrow after LUCAR-G39P infusion.	ThTrough study completion , an average of 2 years after LUCAR-G39P infusion (Day 1)
The recommended Phase II dose (RP2D) for this cell therapy	RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion	Within 30 days after LUCAR-G39P infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LUCAR-G39P cell infusion	Through study completion, an average of 2 years after LUCAR-G39P infusion (Day 1)
Progression-free survival (PFS)	rogression Free Survival (PFS) is defined as the time from the date of first infusion of the LUCAR-G39P to the first documented disease progression (according to Lugano 2014) or death (due to any cause), whichever occurs first	Through study completion, an average of 2 years after LUCAR-G39P infusion (Day 1)
Overall Survival (OS)	Overall Survival (OS) is defined as the time from the date of first infusion of LUCAR-G39P to death of the subject	Through study completion, an average of 2 years after LUCAR-G39P infusion (Day 1)
Time to Response (TTR)	Time to Response (TTR) is defined as the time from the date of first infusion of LUCAR-G39P to the date of the first response evaluation of the subject who has met all criteria for CR or PR	Through study completion, an average of 2 years after LUCAR-G39P infusion (Day 1)
Duration of Response (DoR)	Duration of Remission (DoR) is defined as the time from the first documentation of remission (CR or PR) to the first documented relapse evidence of the responders.	Through study completion, an average of 2 years after LUCAR-G39P infusion (Day 1)
Immunogenicity assessment of LUCAR-G39P cells	The incidence of Anti- LUCAR-G39P antibody in patients who received LUCAR-G39P cells infusion	Through study completion, an average of 2 years after LUCAR-G39P infusion (Day 1)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Nanjing Legend Biotech Co.
• Investigators: Principal Investigator: Jianyong Li, PhD,MD, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: February 18, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Actual): March 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: LB2304-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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