CART84

Table of contents

• What is CART84?
• How does CART84 work?
• Which conditions is CART84 being studied for?
• How is CART84 given?
• What do the clinical trials show?
• What side effects are known?

What is CART84?

CART84 is an investigational cell therapy, meaning it is not yet authorised as a medicine. It belongs to a class of treatments called chimeric antigen receptor (CAR) T-cell therapies, which use a patient's own immune cells that have been modified in the laboratory to recognise and attack cancer cells.^[2] The product name under which it is being developed is GYA01, and the company responsible for the product is Gyala Therapeutics.^[1] In registry records, CART84 is described as a structurally diverse substance of cell therapy origin, given as a dispersion for intravascular use.^[1] It has no marketing authorisation in the product records and remains an investigational substance.^[1]

How does CART84 work?

CART84 is a first-in-class CAR T-cell therapy that targets a protein called CD84.^[2] CD84 is found at high levels on leukemic blasts — the abnormal cells that drive AML and T-ALL — but has limited expression on hematopoietic stem progenitor cells (HSPC), which are the healthy cells that give rise to blood cells. It is largely absent in healthy human tissues.^[2] By directing modified T cells against CD84, CART84 aims to eliminate leukemic cells while sparing healthy blood-forming stem cells, which may reduce the risk of damage to the bone marrow.^[2] In laboratory and animal studies, CART84 showed potent cytotoxicity against AML and T-ALL cells and eliminated primary leukemic blasts, while showing low cytotoxicity against healthy CD34-positive HSPC.^[2]

Which conditions is CART84 being studied for?

CART84 is being investigated in two blood cancers:

• Relapsed or refractory acute myeloid leukemia (AML) — a cancer of the blood and bone marrow that has come back after treatment or has not responded to previous therapy.^[1]
• Relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) — a fast-growing cancer of T-cell lymphocytes that has returned or resisted treatment.^[1]

Both conditions are described in the source as having limited treatment options, and CAR T-cell therapies are seen as offering significant potential for patients with these relapsed or refractory forms.^[2]

How is CART84 given?

CART84 is administered by intravascular use, meaning it is given directly into a blood vessel, as a dispersion.^[1] The trial record describes the intervention as an infusion of CART84.^[1] No further details on dose or infusion schedule are reported in the available sources.

What do the clinical trials show?

One clinical trial of CART84 is registered: a Phase 1/2a study with the EU trial number 2024-519966-31-00.^[1] It is an interventional study with a planned enrollment of 39 participants, and its current status is authorised.^[1] The trial has two parts. Phase 1 is a dose-escalation stage to evaluate safety and tolerability and to determine the dose to be used in Phase 2.^[1] Phase 2a evaluates clinical efficacy at the recommended Phase 2 dose, measured as the overall response rate (ORR) — the proportion of patients achieving complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or morphological leukemia-free state (MLFS).^[1]

The primary outcome for Phase 1 is the frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after CART84 infusion, graded using CTCAE version 5.0 and the ASTCT grading system for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).^[1] Adverse events of special interest include infusion reactions, tumor lysis syndrome, CRS, ICANS, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, prolonged cytopenia, hepatitis B reactivation, infections meeting SAE criteria, and second neoplasms.^[1] For Phase 2a, the primary outcome is the proportion of patients achieving ORR at day 30 after the first infusion of CART84, assessed according to European Leukemia Net (ELN) 2022 guidelines.^[1]

What side effects are known?

The preclinical source does not report side effects from human studies, as the trial is not yet reporting results. However, the trial protocol lists adverse events of special interest that will be monitored, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, tumor lysis syndrome, prolonged cytopenia, and infections meeting serious adverse event criteria.^[1] In laboratory models, CART84 showed low cytotoxicity against healthy CD34-positive hematopoietic stem progenitor cells, suggesting a low risk of myelotoxicity, but this has not yet been confirmed in patients.^[2]