A Study of JNJ-90014496 in Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

A Phase Ib Multicenter, Open-Label, Study of JNJ-90014496, an Autologous CD19/CD20 Bi-specific CAR-T Cell Therapy in Adult Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

This is a Phase Ib multicenter, open-label study of JNJ-90014496, an autologous bi-specific chimeric antigen receptor (CAR) T-cell therapy, targeting both cluster of differentiation (CD) CD19 and CD20 for the treatment of adult participants with relapsed or refractory B-Cell non-Hodgkin lymphoma (r/r B-NHL).

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory B Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Biological: JNJ-90014496

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact, M.D.; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • Recruiting
    • St Vincents Hospital Melbourne
  • Melbourne, Australia, 3004
    • Recruiting
    • The Alfred Hospital
  • Murdoch, Australia, 6150
    • Recruiting
    • Fiona Stanley Hospital
  • Waratah, Australia, 2298
    • Recruiting
    • Calvary Mater Newcastle Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute
  • New Jersey
    • Piscataway, New Jersey, United States, 08854
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • North Carolina
    • Charlotte, North Carolina, United States, 28001
      • Recruiting
      • Levine Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center
  • Texas
    • Austin, Texas, United States, 78704
      • Recruiting
      • St. David's South Austin Medical Center
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Texas Transplant Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent
• Diagnosis of mature aggressive large B cell non-Hodgkin lymphoma or follicular lymphoma
• Tumor must be histologically confirmed cluster of differentiation (CD)19 and/or CD20 positive
• Must have relapsed or refractory disease with the following indications for each histologic subtype: Mature aggressive large B cell non-Hodgkin lymphoma (NHL) and follicular lymphoma Grade 3b: Participants must have >= 2 lines of systemic therapy, or >= 1 line of systemic therapy for participants who are ineligible for autologous stem cell transplant; Follicular lymphoma Grade 1-3a and marginal zone lymphoma: Participants must have >= 2 prior lines of anti-neoplastic systemic therapy. Participants also must have prior exposure to an anti-CD20 monoclonal antibody
• Measurable disease as defined by Lugano 2014 classification
• Eastern cooperative oncology group (ECOG) performance status of either 0 or 1

Exclusion Criteria

• Diagnosis of Human herpes virus (HHV) 8-positive diffuse large B Cell lymphoma (DLBCL)
• Prior allogeneic hematopoietic stem cell transplantation (HSCT)
• Autologous stem cell transplant within 12 weeks of chimeric antigen receptor (CAR) T cell infusion
• Uncontrolled active infections
• History of deep vein thrombosis or pulmonary embolism within six months of infusion (except for line associated deep vein thrombosis [DVT])
• History of stroke, unstable angina, myocardial infarction, congestive heart failure New York Heart Association (NYHA) Class III or IV, severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of screening
• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or neurodegenerative disorder
• Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
• Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones)

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: JNJ-90014496; Participants will receive intravenous (IV) infusion of autologous JNJ-90014496 on Day 1.	Biological: JNJ-90014496; JNJ-90014496, an autologous bi-specific chimeric antigen receptor (CAR) - T cell therapy targeting Cluster of differentiation (CD)19 and CD20.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the Recommended Phase 2 Dose (RP2D) of JNJ-90014496 in Participants with Relapsed or Refractory B-cell non-Hodgkin lymphoma (B-NHL)	Based on the assessment of DLTs rates and overall safety profile.	Up to 24 months
Occurrence of Adverse Events (AEs) [Safety and Tolerability]	Occurrence of any AEs, including dose limiting toxicities (DLTs).	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Evaluation of JNJ-90014496	JNJ-90014496 blood levels will be reported.	Up to 24 months
Overall Response (OR)	Complete response (CR) and partial response (PR) will be assessed by Lugano 2014 guidelines.	Up to 24 months
Time to Response (TTR)	The time from the date of JNJ-90014496 infusion to the first documented CR or PR will be assessed by Lugano 2014 guidelines.	Up to 24 months
Duration of Response (DOR)	The time from the first documented CR or PR to relapse or death, whichever occurs first will be assessed by Lugano 2014 guidelines.	Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The time from the date of C-CAR039 infusion to the date of first documented disease progression or death	Throughout the first 12 months follow up period completion (3 years)
Overall survival (OS)	The time from the date of C-CAR039 infusion to the date of death	Throughout the first 12 months follow up period completion (3 years)
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 24 months
Blood cytokines changes	Blood cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) changes over time in blood	up to 24 months
Anti-drug (C-CAR039) antibody	Presence of serum anti-drug (C-CAR039) antibody	Up to 24 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Collaborators: City of Hope Medical Center
• Investigators: Principal Investigator: John Baird, M.D., City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): October 28, 2028

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 13, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: CD19/CD20-directed CAR-T Cells
• 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: 90014496LYM1001 (Other Identifier: Janssen Research & Development, LLC); 2023-506267-33-00 (Registry Identifier: EUCT number); 2023-506267-33 (EudraCT Number)

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