A Phase 2 Study of Firi-cel in Patients With Relapsed/Refractory Large B-cell Lymphoma (FIRCE-1)

An Open-label, Multicenter Phase 2 Study Evaluating the Efficacy and Safety of Firi-cel, a CD22-directed Autologous Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With Relapsed/Refractory Large B-Cell Lymphoma After CD19-directed CAR T-cell Therapy

This is a prospective, open-label, multi-center clinical study designed to evaluate the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of firicabtagene autoleucel (firi-cel), a CD22-directed autologous Chimeric Antigen Receptor (CAR) T-cell therapy for the treatment of relapsed or refractory large B-cell lymphoma (LBCL).

Study Overview

• Status: Terminated
• Conditions: Cancer; Relapsed/Refractory Large B-cell Lymphoma (LBCL)
• Intervention / Treatment: Drug: Fludarabine (Conditional therapy); Drug: Cyclophosphamide Monohydrate (Conditional therapy); Drug: firi-cel (Experimental drug)

Detailed Description

Firicabtagene autoleucel (firi-cel) is an autologous CAR T-cell therapy targeting CD22, a common B-cell antigen widely expressed in LBCL. This Phase 2 study is designed to evaluate the safety and the efficacy of firi-cel in patients with R/R LBCL that has progressed after CD19-directed CAR T-cell therapy. The study is designed to treat up to 123 patients with a single infusion of firi-cel.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas Medical Sciences
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Division of Hematology Oncology
    • Stanford, California, United States, 94305
      • Stanford University Hospital and Clinics
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612-941
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hopitals & Clinics
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center Research Institute, Inc
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine in St. Louis
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10016
      • New York University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9020
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center
    • Seattle, Washington, United States, 98109
      • UW-Fred Hutchinson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-1222
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Aged ≥18 years
• Relapsed or refractory, histologically confirmed large B-cell lymphoma.
• Must have relapsed or refractory diseae after last therapy.
• For enrollment in cohort 1, patients must have previously received a CD19-directed CAR T-cell therapy
• For enrollment in cohort 3, patients must have received at least two prior lines of therapy including a bispecific T-cel engaging antibody therapy.
• Must have at least one radiographically measurable lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematological, renal, and liver function
• Willing and able to remain within 1 hour of the treating center for at least 4 weeks after infusion.

Key Exclusion Criteria:

• Clinically significant concurrent medical illness
• Active fungal, bacterial, viral or other infection.
• Prior allogeneic stem cell transplant or allogeneic cell therapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Drug (Cohort 1); Single infusion of firi-cel following conditioning chemotherapy	Drug: Fludarabine (Conditional therapy); Lymphodepletion chemotherapy; Drug: Cyclophosphamide Monohydrate (Conditional therapy); Lymphodepletion chemotherapy; Drug: firi-cel (Experimental drug); Investigational agent
Experimental: Experimental Drug (Cohort 2: non-conforming product); Single infusion of firi-cel following conditioning chemotherapy (patients in this cohort will receive non-conforming firi-cel that is deemed safe to administer).	Drug: Fludarabine (Conditional therapy); Lymphodepletion chemotherapy; Drug: Cyclophosphamide Monohydrate (Conditional therapy); Lymphodepletion chemotherapy; Drug: firi-cel (Experimental drug); Investigational agent
Experimental: Experimental Drug (Cohort 3); Patients with relapsed or refractory Large B-cell lymphoma who have previously been treated with bispecific T-cell engaging antibody therapy will receive a single infusion of firi-cel following conditioning chemotherapy.	Drug: Fludarabine (Conditional therapy); Lymphodepletion chemotherapy; Drug: Cyclophosphamide Monohydrate (Conditional therapy); Lymphodepletion chemotherapy; Drug: firi-cel (Experimental drug); Investigational agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate - Blinded independent review	Percentage of patients with complete or partial response determined by a blinded independent review committee	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate - Investigator assessment	Percentage of patients with complete or partial response determined by the investigator	Up to 24-months
Complete response rate	Percentage of patients who achieve a Complete Response determined by independent review committee and investigators assessment	Up to 24-months
Duration of response	Duration of response (the time from the date of the first occurrence of complete response or partial response to the date of progression, relapse, or death from any cause) determined by independent review committee and investigators	Up to 24-months
Duration of complete response	Time from the date of the first occurrence of CR to the date of progression, relapse, or death from any cause determined by independent review committee and investigators.	Up to 24-months
Progression-free survival	Progression-free survival (the time from CRG-022 infusion until the first occurrence of disease progression or relapse) determined by independent review committee and investigator assessment	Up to 24-months
Overall Survival	Overall Survival (the period from the date of CRG-022 infusion until the date of death from any cause) documented by the Investigator.	Up to 24-months
Incidence rate of adverse events	Percentage of patients with treatment-related adverse events is assessed by CTCAEv5.0, CRS, ICANS, and IEC-HS graded by ASTCT criteria.	From Screening up to 15 years at protocol-defined timepoints

Collaborators and Investigators

• Sponsor: CARGO Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Actual): April 4, 2025
• Study Completion (Actual): April 4, 2025

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Cell Therapy; Lymphoma; Lymphoma, Non-Hodgkin; CAR T-cell therapy; CD-22 Expressing Tumor; Adoptive Immunotherapy; CAR T; Lymphoma, B-Cell; Cellular Immuno-therapy; Chimeric Antigen Receptor; CD22; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Primary Mediastinal B-cell; Lymphoma, Transformed; Lymphoma, Transformed Non-Hodgkin; CRG-022; FIRCE-1; firicabtagene autoleucel; firi-cel
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: CRG-022-101

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
• product manufactured in and exported from the U.S.: No