FDA Pauses iMMagine-1 Study of CART-ddBCMA in Relapsed/Refractory Multiple Myeloma

The FDA has placed a clinical hold on a study (NCT05396885) of a BCMA-specific chimeric antigen receptor (CAR)-modified T-cell therapy, CART-ddBCMA, which is being developed for the treatment of relapsed or refractory multiple myeloma (RRMM).¹

CART-ddBCMA is an investigational new drug which has also been granted fast track, orphan drug, and regenerative medicine advanced therapy designations by the FDA for the treatment of RRMM.

On June 16, 2023, a patient undergoing treatment with CART-ddBCMA died. According to the drug’s developer, Arcellx, Inc, constraints related to bridging therapy could be a factor that led to the patient’s death. The company plans to work with the FDA to alter the protocol of the phase 2 iMMagine-1 study, so that it aligns with clinical practice. Arcellx has been granted clearance by the FDA to continue dosing CART-ddBCMA in patients who have had lymphodepleting therapy.

“The safety and well-being of patients enrolled in our studies is our top priority," said Rami Elghandour, chairman and chief executive officer of Arcellx, in a press release.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,” Elghandour added.

In iMMagine-1, a pivotal, open-label, multicenter study, roughly 110 patients with RRMM will be enrolled. Patients in the study will be administered a single dose of CART-ddBCMA 115±10 x 10^-6 CAR-positive CART-ddBCMA cells via intravenous infusion.²

The primary goal in the iMMagine-1 study is overall response rate. The secondary end points to be explored in the study include stringent complete response rate, duration of response, very good partial response, time to initial response, progression-free survival, overall survival, the safety profile of CART-ddBCMA as determined by adverse events (AEs), pharmacokinetics, anti- CART-ddBCMA antibodies, and health-related quality-of-life.

To be eligible for inclusion, patients must be 18 years of age or older with RRMM and documented measurable disease. Patients enrolled in the study are required to have a ECOG performance status of 0-1, a life expectancy of at least 12 weeks, and adequate organ function. Prior to treatment in the study, AEs in patients must be resolved to at least grade 1.

The study excludes patients who were previously treated with prior systemic therapy for multiple myeloma within 14 days of starting study treatment, high-dose systemic therapy or immunosuppressives therapy within 14 days, previous treatment with a gene-modified cellular immune therapy, BCMA-directed therapy, or autologous stem cell transplantation within 3 months. Patients are also excluded based on their disease history or comorbidities that may interfere with the effectiveness of treatment.

“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,” said Elghandour, in the press release.¹

_REFERENCES:

_{1. Arcellx announces clinical hold for its IMMagine-1 phase 2 clinical program. News release. Arcellx, Inc. June 19, 2023. Accessed June 20, 2023. https://tinyurl.com/2xbmm34d}

_{2. Study of CART-ddBMCA in relapsed or refractory multiple myeloma (iMMagine-1). ClinicalTrials.gov. Updated March 22, 2023. Accessed June 20, 2023. https://clinicaltrials.gov/ct2/show/NCT05396885?term=iMMagine-1&draw=2&rank=1}