Patient Death Prompts Hold on Arcellx’s CART-ddBCMA for R/R Multiple Myeloma


The company believes that limitations on bridging therapies were a contributing factor to the death.

The FDA has placed a clinical hold on Arcellx’s investigational new drug application for CART-ddBCMA after a patient with relapsed/refractory multiple myeloma (rrMM) treated in the phase 2 iMMagine-1 clinical trial (NCT05396885) died.1

CART-ddBCMA is a BCMA-specific chimeric antigen receptor (CAR)-modified T-cell therapyutilizing the company's novel BCMA-targeting binding domain, novel synthetic proteins designed to bind specific therapeutic targets. The FDA has previously granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations to CART-ddBCMA.

The FDA has cleared Arcellx to continue dosing patients that have undergone lymphodepletion amongst the hold. Arcellx is working with the FDA to expand options for patients to be consistent with current clinical practices, especially focusing on expanding current limitations with bridging therapy, which the company believes were a contributing factor to the death.

"The safety and well-being of patients enrolled in our studies is our top priority," Rami Elghandour, chairman and chief executive officer, Arcellx, said in a statement.1 " In coordination with our investigators, data safety monitoring board, and our partners at Kite Pharma, we are working with FDA to address the clinical hold. The expansion of bridging therapy regimens is consistent with what's currently available in clinical practice and is in the best interest of patients. Additionally, we continue to evaluate other potential improvements to the study. We remain confident that CART-ddBCMA is a potential best-in-class therapy for the treatment of patients with rrMM based on the clinical profile observed in the patients dosed to date across our studies. The drug product release characteristics from iMMagine-1 are consistent with those from our Phase 1 study. The manufacturing success rate remains 100% while ramping Lonza, our cell therapy manufacturer, to full scale. Fourteen clinical sites have been opened and study enrollment is tracking to our expectations. We look forward to resolving this matter expeditiously and to continue to advance our therapy to the benefit of patients suffering from rrMM."

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The multicenter, open-label iMMagine-1 trial is primarily evaluating overall response rate (ORR) by 24 months. Secondary endpoints include safety, depth of disease response, duration of response, and overall survival.

The most recent data on CART-ddBCMA, from its phase 1 study (NCT04155749), were presented in a poster at the 64th Annual American Society of Hematology (ASH) Meeting, held December 10-13, 2022, in New Orleans, Louisiana, by investigator Matthew J. Frigault, MD, assistant director, Cellular Therapy Service at Mass General Cancer Center, and instructor, Harvard Medical School.2

At this time, the therapy showed a favorable safety profile and in 38 evaluable patients, ORR was 100%. Complete response (CR) or stringent CR (sCR) rate was 71%, with a very good partial response (VGPR) rate of 18%.2 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%. The progression-free survival rate was 91.8% at 6 months, 72.7% at 12 months, and 64.6% at 18 months. Of the 27 patients evaluable for minimal residual disease (MRD), 89% achieved negativity.

“Very rarely in a first-in-human study, do you get a home run on your first patient and keep going. So you know, in some ways, this was a Grand Slam,” Frigault told CGTLive at the ASH meeting.

1. Arcellx announces clinical hold for its iMMagine-1 phase 2 clinical program. News release. Arcellx. June 19, 2023.
2. 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.
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