FDA Lifts Partial Clinical Hold on Arcellx’s Trial for Multiple Myeloma CAR-T CART-ddBCMA


The partial clinical hold was originally placed in June 2023 in relation to the death of a patient participating in the trial.

The FDA has lifted its partial clinical hold on the phase 2 IMMagine-1 clinical trial (NCT05396885) evaluating CART-ddBCMA, an investigational autologous chimeric antigen receptor (CAR) T-cell therapy intended to treat relapsed/refractory (r/r) multiple myeloma (MM).1

The partial clinical hold was originally placed in June 2023 in relation to the death of a patient participating in the trial.2 Arcellx has noted that CART-ddBCMA was administered to this patient in the trial even though the patient had become ineligible according to the trial protocol.1 Furthermore, the management of the patient after administration of the CAR-T was also not consistent with the study’s protocol. Following this, Arcellx has made changes to the study protocol with regard to prevention and management of adverse event (AE) risk, come into agreement regarding these changes with the FDA, and retrained clinical trial sites. At the time the partial hold was placed, the company stated its view that the limitations on bridging therapy in the original study protocol may have contributed to the patient’s death.2 The new protocol changes approved by the FDA now include expanded options for bridging therapy in the study.1

"We have worked closely with FDA to expeditiously resolve the clinical hold and we thank them for their collaboration and dialogue throughout this process," Rami Elghandour, the chairman and CEO of Arcellx, said in a statement.1 "During the review process, we updated our trial protocol, and were pleased that FDA allowed for expanded bridging therapies, which better aligns our protocol with current clinical practice. As a key step to enhancing protocol adherence related to the prevention and management of the risk of AEs, we retrained clinical sites. Importantly, during the partial clinical hold, FDA approved dosing of all 17 patients who had been enrolled but not yet dosed prior to the hold, minimizing treatment disruption for patients and clinicians.”

CART-ddBCMA is Arcellx’s lead product candidate and is being co-developed together with Kite Pharma under a global strategic collaboration agreement in which Kite will assist with development and commercialization in the United States and carry out commercialization activities in other countries. The therapy uses a novel synthetic binding domain referred to as a D-Domain to target B-cell maturation antigen (BCMA).3

In addition to IMMagine-1, CART-ddBCMA is also being evaluated in a phase 1 clinical trial (NCT04155749) in the same indication. Arcellx previously presented results from the phase 1 study at the 64th Annual American Society of Hematology (ASH) Meeting, held December 10-13, 2022, in New Orleans, Louisiana. Among the 38 patients evaluable (minimum follow-up, 1 month), the overall response rate measured by International Myeloma Working Group (IMWG) criteria was 100% and the complete response (CR) or stringent CR (sCR) rate was 71%, with a very good partial response (VGPR) rate of 18%.3,4 Among patients with at least 12 months of follow-up (n = 25), the CR/sCR rate was 80% and VGPR was 12%; among patients with at least 18 months of follow-up (n = 16), the CR/sCR rate was 81% and the VGPR rate was 6%.

“We and our partners at Kite remain confident in CART-ddBCMA's potential as a best-in-class therapy for the treatment of patients with rrMM given the totality of data to date across our studies,” Elghandour continued.1 “We have a strong balance sheet funding operations through biologics license application filing and into 2026. We look forward to presenting data from our phase 1 study later this year as well as preliminary data from the iMMagine-1 study in the second half of 2024. Additionally, we continue to expect commercial launch of CART-ddBCMA to be in 2026."

1. Arcellx announces partial clinical hold lifted on IMMagine-1 phase 2 clinical program and reports second quarter financial results. News release. Arcellx, Inc. August 14, 2023. Accessed August 15, 2023. https://ir.arcellx.com/news/news-details/2023/Arcellx-Announces-Partial-Clinical-Hold-Lifted-on-iMMagine-1-Phase-2-Clinical-Program-and-Reports-Second-Quarter-Financial-Results/default.aspx
2. Arcellx announces clinical hold for its iMMagine-1 phase 2 clinical program. News release. Arcellx, Inc. June 19, 2023. Accessed August 15, 2023. https://www.prnewswire.com/news-releases/arcellx-announces-clinical-hold-for-its-immagine-1-phase-2-clinical-program-301854767.html
3. Frigault M, Rosenblatt JR, Dhakal, B, et al. Phase 1 Study of CART-Ddbcma for the Treatment of Subjects with Relapsed and /or Refractory Multiple Myeloma. Presented at: 2022 ASH Annual Meeting. December 10-13, 2022; New Orleans, LA. Abstract 33132.
4. Arcellx announces continued robust long-term responses from its CART-Ddbcma phase 1 expansion trial in patients with relapsed or refractory multiple myeloma and additional pipeline progress. News release. Arcellx, Inc. December 9, 2022. Accessed August 15, 2023. https://ir.arcellx.com/news/news-details/2022/Arcellx-Announces-Continued-Robust-Long-Term-Responses-from-its-CART-ddBCMA-Phase-1-Expansion-Trial-in-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma-and-Additional-Pipeline-Progress/default.aspx
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