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
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)
Westmead Hospital
Westmead, New South Wales, Australia
RECRUITINGPeter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGHospital MD Anderson
Madrid, Spain
RECRUITINGNumber of Participants With Treatment-emergent Adverse Events
Number of Participants With Adverse Events as Assessed by CTCAE v5.0
Time frame: 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
Time frame: Baseline, up to Day 29
Number of Participants Experiencing Cytokine Release Syndrome (CRS)
Number of participants experiencing Cytokine Release Syndrome (CRS)
Time frame: Baseline, up to Day 29
Number of Participants Experiencing Immune Effector Cell Neurotoxicity (ICANS)
Number of participants experiencing Immune Effector Cell Neurotoxicity (ICANS)
Time frame: 28 Days
Number of Participants Experiencing dose-limiting toxicities (DLTs)
Number of participants experiencing dose-limiting toxicities (DLTs)
Time frame: 28 Days
Levels of Vector Ribonucleic Acid (RNA) Genomes in Blood Over Time
Time frame: Baseline, up to Day 29
Levels of Transgene Deoxyribonucleic Acid (DNA) Copies in Blood Over Time
Time frame: Baseline, up to Day 29
Levels of CD20-targeting Chimeric Antigen Receptor (CAR20) Positive T Cells in Blood Over Time
Time frame: Baseline, up to Day 29
Levels of Natural Killer (NK) Cells in Blood Over Time
Time frame: Baseline, up to Day 29
Number of Participants with CAR20-positive Cells in Accessible Tumour Tissue Over Time
Time frame: Baseline, up to Day 29
Change in the Levels of Lymphocyte Subsets Including B-cell Counts Over Time
Time frame: Baseline, up to Day 29
Objective Response Rate (ORR) as Determined by Investigator Assessment
Time frame: Day 90
Objective Response Rate (ORR) as Determined by Investigator Assessment
Time frame: Year 1
Objective Response Rate (ORR) as Determined by Investigator Assessment
Time frame: Year 2
Objective Response Rate (ORR) as Determined by Investigator Assessment
Time frame: Year 5
Complete Response (CR) Rate as Determined by Investigator Assessment
Time frame: Day 90
Complete Response (CR) Rate as Determined by Investigator Assessment
Time frame: Year 1
Complete Response (CR) Rate as Determined by Investigator Assessment
Time frame: Year 2
Complete Response (CR) Rate as Determined by Investigator Assessment
Time frame: Year 5
Duration of response (DOR) as Determined by Investigator Assessment
Time frame: Up to 5 years
Progression Free Survival (PFS) as Determined by Investigator Assessment
Time frame: Up to 5 years
Overall Survival (OS) as Determined by Investigator Assessment
Time frame: Up to 5 years
Number of Participants with Cytokine Release Syndrome (CRS)
Time frame: Up to 5 years
Number of Participants with Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)
Time frame: Up to 5 years
Duration of Cytokine Release Syndrome (CRS)
Time frame: Up to 5 years
Duration of ICANS
Time frame: Up to 5 years
Number of Participants with Vector-derived Replication Competent Lentivirus (RCL) Through Year 5
Time frame: Up to 5 years
Assessment of Humoral Immunity: Number of Participants with Anti-CAR and Anti-vector Antibodies Over Time
Time frame: 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
Time frame: Up to 5 years
Assessment of Vector Shedding: Number of Participants with Vector Shedding in Saliva, Faeces, and Urine Over Time
Time frame: Up to 5 years
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