The cell therapy is the first to come out of the company’s proprietary ARC-SparX platform.
Biotechnology company Arcellx announced that it has dosed its first patient in the phase 1, open-label clinical trial of ACLX-001, a CAR T-cell therapy born out of the firm’s ARC-SparX cell therapy platform that will be evaluated in patients with relapsed or refractory multiple myeloma (r/r MM).
The universal ARC-SparX cell therapy platform is comprised of soluble protein antigen-receptor X-linkers (SparX) proteins that are engineered to target BCMA on myeloma cells. This works in conjunction with antigen-receptor complex-T (ARC-T) cells that are separately dosed and only active when engaged with a SparX protein that is bound to a myeloma cell. These cells and proteins utilize Arcellx’s novel synthetic binding scaffold, D-Domain, which can potentially enable higher transduction efficiency, high cell surface expression, and low tonic signaling.
The phase 1, proof of concept, dose-escalation study (NCT04155749) will assess up to 65 participants in 2 treatment arms: (1) CART-ddBCMA and (2) SPRX001 and ARC-T cells. Based on pharmacokinetic data, a matrix escalation of either ARC-T cells, SparX-001, or both may be escalated during the trial. Primary outcomes are incidence of treatment-emergent adverse events, including dose-limiting toxicity, and determination of the recommended phase 2 dose over 24 months of follow-up. Secondary outcomes, also assessed over 24 months, are best overall response based on International Myeloma Working Group (IMWG) Consensus Criteria, IMWG-based objective response rate, and in vivo expansion and persistence of the investigational agent in peripheral blood and target tissues.
"ARC-SparX provides physicians with the ability to control the dose and frequency of SparX administration. This may allow the physician to better manage toxicities associated with traditional CAR-T therapies, potentially increasing patient access to this treatment option,” said Binod Dhakal, MD, MS, trial investigator and associate professor of medicine, Division of Hematology/Oncology, Medical College of Wisconsin.
In addition to ACLX-001, Arcellx is also planning to assess another ARC-SparX program—ACLX-002—in a phase 1 program in r/r acute myeloid leukemia and high-risk myelodysplastic syndrome in the second half of 2022.
The company also recently published results from its phase 1 study on its lead program, CART-ddBCMA, which demonstrated a 100% overall response rate and nearly 70% complete response rate in patients with r/r MM.
In an interview with CGTLive, Arcellx chairman and CEO Rami Elghandour said “When you transduce your cells using a viral vector to produce a CAR T therapy, a higher percentage of our cells are CAR-positive, or, in effect, they would be tumor-identifying and killing. As a result of having that higher transduction efficiency, we can, in effect, have a lower overall total cell dose, which we believe can contribute to having a therapy that is both effective and more tolerated, or the potential for a better safety profile."
"These are obviously early results but they're very encouraging results," he continued. "We have an upcoming presentation at the ASCO meeting in June where we're excited to show further results."