FDA Places Clinical Hold on BCMA-Directed Modified CAR T-Cell Therapy in Multiple Myeloma

Author(s):

The FDA has placed a hold on the clinical program for the investigational new drug CART-ddBCMA for the treatment of patients with relapsed/refractory multiple myeloma.

The FDA has placed a hold on the clinical program for the investigational new drug CART-ddBCMA for the treatment of patients with relapsed/refractory multiple myeloma, according to an announcement from Arcellx, Inc.

The clinical hold was received following documentation of a patient death. The reason for the death was not stated; however, the company believes limitations on bridging therapy may have been a contributing factor. As such, the company is working with the FDA to update the trial protocol to allow treatment that is more reflective of current clinical practice options.

Patients who have already undergone lymphodepletion will be allowed to continue to be dosed in the trial.

“The safety and well-being of patients enrolled in our studies is our top priority,” Rami Elghandour, chairman and chief executive officer of Arcellx, said in a press release. “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 relapsed/refractory multiple myeloma based on the clinical profile observed in the patients dosed to date across our studies. The drug product release characteristics from [the phase 2] iMMagine-1 [trial (NCT05396885)] 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,” Elghandour said.

CART-ddBCMA is a BCMA-specific CAR-modified T-cell therapy under evaluation in the phase 2 iMMagine-1 trial for the treatment of patients with relapsed/refractory multiple myeloma. The agent, designed with Arcellx’s proprietary BCMA-targeting binding domains, uses novel synthetic proteins designed to bind specific therapeutic targets.

Previously, the FDA granted fast track, orphan drug, and regenerative medicine advanced therapy designations to CART-ddBCMA.

The pivotal, open-label, multicenter iMMagine-1 trial will evaluate overall response rate over a 24-month period as the primary end point. In addition to safety, secondary end points will include depth of response, duration of response, and overall survival over a 24-month period.

“We look forward to resolving this matter expeditiously and to continue to advance our therapy to the benefit of patients suffering from relapsed/refractory multiple myeloma,” Elghandour concluded.