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

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

Eligibility

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.

Conditions3

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