FDA puts CART-ddBCMA Phase 2 trial on hold after patient’s death

Move pauses iMMagine-1 trial of cell therapy in up to 110 adults with rrMM

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has placed a hold on clinical testing of CART-ddBCMA, a cell therapy that Arcellx and Kite Pharma are co-developing for people with relapsed and refractory multiple myeloma (rrMM), following the death of a patient enrolled in the trial.

The move pauses the ongoing, pivotal Phase 2 iMMagine-1 trial (NCT05396885) that’s testing the therapy in up to 110 adults with rrMM who received at least three prior therapy lines, including a proteasome inhibitor, an immunomodulatory agent, and a CD38 inhibitor.

If positive, two-year safety and efficacy results will be used to support regulatory applications seeking the treatment’s approval for rrMM patients.

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Arcellx cleared to dose patients who underwent immune-depleting regimens

The FDA, however, has given Arcellx the go-ahead to dose patients who have already undergone lymphodepletion — immune-depleting regimens given before CART-ddBCMA administration.

“The safety and well-being of patients enrolled in our studies is our top priority,” Rami Elghandour, chairman and CEO of Arcellx, said in a company press release. “In coordination with our investigators, data safety monitoring board (DSMB), and our partners at Kite Pharma, we are working with FDA to address the clinical hold.”

“We look forward to resolving this matter expeditiously and to continue to advance our therapy to the benefit of patients suffering from rrMM,” he added.

Arcellx’s CART-ddBCMA is a chimeric antigen receptor (CAR) T-cell therapy that involves collecting a patient’s immune T-cells, then engineering them with a receptor that directs the cells toward BCMA, a protein highly present on myeloma cells. The engineered cells are then re-infused into the patient to fight the cancer.

Early this year, Arcellx and KitePharma closed an agreement to co-develop and co-commercialize CART-ddBCMA for rrMM patients.

Arcellx stated that it believes the recent patient death which prompted this clinical hold was due in part to limitations on bridging therapies, referring to the anti-cancer treatments given between the initial collection of T-cells and the administration of the engineered therapy — a process that usually takes at least a few weeks.

The company did not provide further details on the perceived limitations, but said it would be working with the FDA to expand the trial protocol to give patients more options that are consistent with current clinical practice.

“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 said.

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Phase 1 trial also testing CART-ddBCMA in up to 65 adults with rrMM

CART-ddBCMA is also being tested in up to 65 adults with rrMM in a Phase 1 trial (NCT04155749). Early results of the first 12 evaluable rrMM patients indicated that all responded to treatment after more than six months, and most showed a complete response.

Data on the therapy’s activity in the iMMagine-1 study so far “are consistent with those from our Phase 1 study,” Elghandour said.

“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,” he added.

CART-ddBCMA received fast track, orphan drug, and regenerative medicine advanced therapy designations in the U.S. for the treatment of people with rrMM.