Trial Assessing CAR T-Cell Therapy ACLX-001 in Relapsed/Refractory Multiple Myeloma Begins

Pipeline Report | <b>Pipeline Report: May 2022</b>

Investigators have initiated a phase 1 trial exploring ACLX-001, a novel CAR T-cell therapy using the ARC-SparX platform, in patients with relapsed/refractory multiple myeloma.

Investigators have initiated a phase 1 trial (NCT04155749) exploring ACLX-001, a novel CAR T-cell therapy using the ARC-SparX platform, in patients with relapsed/refractory multiple myeloma (rrMM). The first patient received study treatment in May 2022, according to drug manufacturer Arcellx.1

ARC-SparX is a universal cell therapy platform comprised of soluble protein antigen-receptor X-linker (SparX) proteins designed to target BCMA on myeloma cells. This is combined with a separate dose of antigen receptor complex-T (ARC-T) cells, which are designed to activate only when engaged with a SparX protein that has bound to a myeloma cell. The combination of ARC-T cells and the SparX protein form ACLX-001.2 ARC-T cells and SparX proteins use the Arcellx’s novel synthetic binding scaffold called the D-Domain.

“ACLX-001 is a combination of the SparX ARC-T cells and their complex with the BCMA-positive cells that are mainly present in the myeloma cells. You need to have all 3 [components] for the T cells to get activated, as compared with conventional CAR T-cell therapy, where the CAR T-cell therapy has this BCMA-binding domain antibody that goes and kills the target right away,” Binod Dhakal, MD, MS, associate professor of medicine, Division of Hematology/Oncology, Medical College of Wisconsin, and clinical investigator on the phase 1 trial, said in an interview with OncLive®.

In April 2021, the FDA cleared an investigational new drug application for ACLX-001, based on earlier data from a phase 1 trial investigating CART-ddBCMA, which demonstrated the advantages of the D-Domain.3

The phase 1 trial is a first-in-human, open-label, multicenter, dose escalation study in patients with rrMM who have received at least 3 prior regimens of systemic therapy, including a proteosome inhibitor, immunotherapy, and anti-CD38 antibodies. Eligible patients are also required to have documented measurable disease, adequate organ function, an ECOG performance status of 0 or 1, and a life expectancy of more than 12 weeks.4

Exclusion criteria include active plasma cell leukemia or a history of plasma cell leukemia, a history of severe hypersensitivity to dimethyl sulfoxide, contraindication to fludarabine or cyclophosphamide, severe uncontrolled intercurrent illness or laboratory abnormalities, and active central nervous system (CNS) disease involvement by malignancy or active CNS pathology.

Once enrolled, patients can receive either ARC-T cells, SparX-001, or both, and treatment may be escalated based on clinical correlative data, including pharmacokinetics of SparX-00 and ARC-T expansion.

The primary end points of the trial are the incidence of treatment-emergent adverse effects, including dose-limiting toxicities over 24 months, and the establishment of the recommended phase 2 dose. Secondary end points include best overall response and overall response rate by IMWG consensus criteria, plus in vivo pharmacokinetics.

“This is really unique platform, and for the first time, we are trying to investigate the potential of modulating activity of the CAR T-cell therapy outside the body with this SparX protein,” Dhakal said. “This trial is trying to understand lot of unmet needs in the area of myeloma, and if it works well, it could have a lot of broader application in lots of other cancers.”

The trial is still accruing patients. Initial data from the phase 1 study are expected in 2023.


  1. Arcellx announces dosing of first patient in its phase 1 clinical trial evaluating ACLX-001, the first therapeutic in the dosable and controllable ARC-SparX platform, for the treatment of patients with relapsed or refractory multiple myeloma. News release. Arcellx. May 10, 2022. Accessed May 12, 2022.
  2. Our pipeline. Arcellx. Accessed May 12, 2022.
  3. Arcellx announces FDA clearance of IND application for ACLX-001, a controllable cell therapy utilizing the company’s ARC-SparX platform, for the treatment of multiple myeloma. News release. Arcellx. April 6, 2021. Accessed May 12, 2022.
  4. Master protocol for the phase 1 study of cell therapies in multiple myeloma. Updated February 10, 2022. Accessed May 12, 2022.