A Study to Investigate Safety of INT2104 Infusions in Participants Aged 18 Years of Age and Older Who Have B-cell Cancers That Came Back After Previous Treatment (INVISE)

A Two-Part Open Label Phase 1 Multicentre Study Evaluating the Safety of INT2104 Infusion in Female and Male Participants Aged 18 Years of Age and Older With Refractory/Relapsing B-Cell Malignancies

The purpose of this first-in-human study is to evaluate the safety and tolerability of INT2104 when administered to humans in a broad population of participants with refractory/relapsing B-cell malignancies. Preliminary efficacy information may also be obtained.

INT2104 is a gene therapy delivering a transgene for a chimeric antigen receptor (CAR) specific for CD20 (CAR20). The lentiviral vector is designed to generate CAR T and CAR Natural Killer (NK) cells inside the body following intravenous (IV) administration.

Study details include the following:

• The study duration will be 5 years
• The treatment duration will be a one-time intravenous (IV) infusion of INT2104

Study Overview

• Status: Active, not recruiting
• Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphomas Non-Hodgkin's B-Cell
• Intervention / Treatment: Genetic: INT2104

Detailed Description

This is a non-randomized, open label, multi-site, Phase 1 First in Human (FIH) study split into two parts. The first part (Part A) is a dose escalation and the second part (Part B) will be to confirm the dose.

The aim of the study is to collect data to assess whether the study product, INT2104, is safe and tolerable, to understand how well INT2104 works in the human body and to select the dose to take into a Phase 2 study.

All participants will receive one intravenous (IV) infusion of INT2104.

Each participant in the study will follow the same study treatment schedule and will proceed through the following study periods:

• Screening Period: participant will be assessed for eligibility
• Study Day 1: participants who meet all eligibility criteria will receive INT2104 by a one-time infusion
• Post-treatment Assessment Period: participants will be followed regularly with clinic visits after they receive INT2104

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Spain
  • Madrid, Spain, 28033
    • Hospital MD Anderson

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosed with relapsed/refractory (R/R) B-NHL (Burkitt's lymphoma are eligible for Part B only) confirmed by histology or flow cytometry Note: Bone Marrow involvement is allowed
• B-NHL must have CD20 antigen positive tumour confirmed from a tumour biopsy taken at screening
• Measurable disease at the time of enrolment
• Progression after at least 2 lines of systemic therapy
• Has not received more than one prior marketed CAR-T cell therapy (including tandem or bispecific CAR-T) or other genetically modified T-cell therapy.
• Sex and Contraceptive/Barrier Requirements consistent with local regulations for clinical trials Females: must have negative serum pregnancy test at screening and on Day -1 prior to INT2104 infusion Both sexes: must agree to use highly effective methods, including a barrier method after INT2104 infusion

• Haematological criteria:

  • Absolute lymphocyte count (ALC) ≥300/µL
  • Platelet count ≥50,000/mL
  • Absolute neutrophil count (ANC) ≥500/µL
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Adequate renal, cardiac, hepatic, and lung function

Key Inclusion Part B only

• Diagnosed with relapsed/refractory B-ALL, and with exceptions as detailed in exclusion criteria. Participants with Philadelphia chromosome positive (Ph+) B-ALL disease are eligible.
• B-ALL participants must have CD20 antigen positive leukaemia
• Measurable disease at the time of enrolment
• Participants with Burkitt's lymphoma are eligible for Part B only

Exclusion Criteria:

• Central Nervous System (CNS)-only B-cell malignancy, or B-cell malignancy with R/R secondary CNS involvement.
• Diagnosis or history of chronic lymphocytic leukaemia (CLL) (including large cell [Richter] transformation of CLL) or small lymphocytic lymphoma (SLL)
• Diagnosis or history of cutaneous lymphoma
• History of another primary malignancy that has not been in remission for at least 3 years before signing informed consent (except for: non-melanoma skin cancer, low grade prostate cancer or carcinoma in situ (e.g., cervix, bladder, breast))
• Acute or chronic graft-versus-host disease
• Participant has received donor lymphocyte infusion within 6 weeks prior to INT2104 infusion
• History of autoimmune disease requiring systemic immunosuppression/ systemic disease modifying agents within 2 years before enrolment
• History or presence of CNS disorder
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months before signing informed consent
• Participants has active syphilis, cytomegalovirus (CMV), acute or chronic active hepatitis B, or untreated hepatitis C.
• Participant is Human immunodeficiency virus (HIV) positive.
• Any medical condition likely to interfere with assessment of safety or efficacy of the study treatment
• A vaccine within 4 weeks prior to INT2104 infusion
• Intolerance or severe hypersensitivity reaction to any excipients of the INT2104 product.
• An active fungal, bacterial, viral, or other infection that is uncontrolled or requires antimicrobials at the time of INT2104 infusion.
• Participant is pregnant or nursing.
• In the investigator's judgment, the participant is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation

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: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INT2104 Dose Level 1; Single IV administration of INT2104	Genetic: INT2104; INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)
Experimental: INT2104 Dose Level 2; Single IV administration of INT2104	Genetic: INT2104; INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)
Experimental: INT2104 Dose Level 3; Single IV administration of INT2104	Genetic: INT2104; INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)
Experimental: INT2104 Recommended Dose; Single IV administration of INT2104	Genetic: INT2104; INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)
Experimental: INT2104 Dose Level 4; Single IV administration of INT2104	Genetic: INT2104; INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events	Number of Participants With Adverse Events as Assessed by CTCAE v5.0	Up to 5 years
Number of Participants With Abnormal Clinical Laboratory Values and Physical Examination Results	Number of Participants With abnormal clinical laboratory values as Assessed by CTCAE v5.0	Baseline, up to Day 29
Number of Participants Experiencing Cytokine Release Syndrome (CRS)	Number of participants experiencing Cytokine Release Syndrome (CRS)	Baseline, up to Day 29
Number of Participants Experiencing Immune Effector Cell Neurotoxicity (ICANS)	Number of participants experiencing Immune Effector Cell Neurotoxicity (ICANS)	28 Days
Number of Participants Experiencing dose-limiting toxicities (DLTs)	Number of participants experiencing dose-limiting toxicities (DLTs)	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response (DOR) as Determined by Investigator Assessment	Up to 5 years
Progression Free Survival (PFS) as Determined by Investigator Assessment	Up to 5 years
Overall Survival (OS) as Determined by Investigator Assessment	Up to 5 years
Number of Participants with Vector-derived Replication Competent Lentivirus (RCL) Through Year 5	Up to 5 years
Levels of Vector Ribonucleic Acid (RNA) Genomes in Blood Over Time	Baseline, up to Day 29
Levels of Transgene Deoxyribonucleic Acid (DNA) Copies in Blood Over Time	Baseline, up to Day 29
Levels of CD20-targeting Chimeric Antigen Receptor (CAR20) Positive T Cells in Blood Over Time	Baseline, up to Day 29
Levels of Natural Killer (NK) Cells in Blood Over Time	Baseline, up to Day 29
Number of Participants with CAR20-positive Cells in Accessible Tumour Tissue Over Time	Baseline, up to Day 29
Change in the Levels of Lymphocyte Subsets Including B-cell Counts Over Time	Baseline, up to Day 29
Objective Response Rate (ORR) as Determined by Investigator Assessment	Day 90
Objective Response Rate (ORR) as Determined by Investigator Assessment	Year 1
Objective Response Rate (ORR) as Determined by Investigator Assessment	Year 2
Objective Response Rate (ORR) as Determined by Investigator Assessment	Year 5
Complete Response (CR) Rate as Determined by Investigator Assessment	Day 90
Complete Response (CR) Rate as Determined by Investigator Assessment	Year 1
Complete Response (CR) Rate as Determined by Investigator Assessment	Year 2
Complete Response (CR) Rate as Determined by Investigator Assessment	Year 5
Number of Participants with Cytokine Release Syndrome (CRS)	Up to 5 years
Number of Participants with Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)	Up to 5 years
Duration of Cytokine Release Syndrome (CRS)	Up to 5 years
Duration of ICANS	Up to 5 years
Assessment of Humoral Immunity: Number of Participants with Anti-CAR and Anti-vector Antibodies Over Time	Up to 5 years
Assessment of Cellular Immunity: Number of Participants with Changes in T-cell Enzyme-Linked Immunospot Assay (ELISPOT) and Cytokine Profiles Over Time	Up to 5 years
Assessment of Vector Shedding: Number of Participants with Vector Shedding in Saliva, Faeces, and Urine Over Time	Up to 5 years

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: August 1, 2024
• First Posted (Actual): August 6, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: INT2104-101; 2023-509132-26-00 (Ctis); U1111-1303-9462 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• IPD Plan Description: At this time it is undecided if individual participant data will be made available to other researchers due to the first in human, first in class nature of the study.
• IPD Sharing Time Frame: Access will begin 9 months and end 24 months following the closure of the clinical trial and following article publication.
• IPD Sharing Access Criteria: Redacted study protocol and statistical analysis plan and data may be made available upon request to researchers who provide a methodologically sound proposal. Proposals should be directed to INT2104-101@interiusbio.com. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

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.: Yes