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)

Gilead Sciences

Status and phase

Enrolling

Phase 1

Conditions

Lymphomas Non-Hodgkin's B-Cell

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Treatments

Genetic: INT2104

Study type

Interventional

Funder types

Industry

Identifiers

NCT06539338

INT2104-101

U1111-1303-9462 (Other Identifier)

2023-509132-26-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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

Full 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

Enrollment

34 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

34 participants in 5 patient groups

INT2104 Dose Level 1

Experimental group

Description: