Overview
The purpose of this first-in-human study is to evaluate the safety 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
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
Eligibility
Inclusion Criteria:
- Age 18 or older and capable of giving signed informed consent
- 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