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

NCT06539338 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: INT2104-1012023-509132-26-00U1111-1303-9462
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

Lymphomas Non-Hodgkin's B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Keywords

Gene Therapy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (25)

• 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

Study Arms (5)

INT2104 Dose Level 1

EXPERIMENTAL

Single IV administration of INT2104

Genetic: INT2104

INT2104 Dose Level 2

EXPERIMENTAL

Single IV administration of INT2104

Genetic: INT2104

INT2104 Dose Level 3

EXPERIMENTAL

Single IV administration of INT2104

Genetic: INT2104

INT2104 Dose Level 4

EXPERIMENTAL

Single IV administration of INT2104

Genetic: INT2104

INT2104 Recommended Dose

EXPERIMENTAL

Single IV administration of INT2104

Genetic: INT2104

Interventions

INT2104 GENETIC

INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)

INT2104 Dose Level 1; INT2104 Dose Level 2; INT2104 Dose Level 3; INT2104 Dose Level 4; INT2104 Recommended Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (3)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Hospital MD Anderson

Madrid, 28033, Spain

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2024
• First Posted: August 6, 2024
• Study Start: September 20, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

AU (2); ES (1)