FDA Lifts Hold on Phase 2 CART-ddBCMA Trial in R/R Multiple Myeloma

The FDA originally placed a clinical hold on the investigators’ assessment of CART-ddBCMA in June 2023 following reports of a patient death.

The FDA has lifted its partial clinical hold on the phase 2 iMMagine-1 trial (NCT05396885) evaluating CART-ddBCMA as a treatment for patients with relapsed/refractory multiple myeloma, according to a press release from Arcellx, Inc.¹

The regulatory agency originally placed a clinical hold on the investigators’ assessment of CART-ddBCMA in June 2023 following reports of a patient death.² According to Rami Elghandour, chairman and chief executive officer at Arcellx, developers updated the trial’s protocol to include expanded bridging therapies following discussions with the FDA. Additionally, investigators retrained clinical sites to enhance protocol adherence related to managing and minimizing the risk of adverse effects (AEs). Moreover, the agency approved dosing of 17 patients who had been enrolled but did not yet receive study treatment before the clinical hold.

“We have worked closely with FDA to expeditiously resolve the clinical hold and we thank them for their collaboration and dialogue throughout this process,” Elghandour said. “We…remain confident in CART-ddBCMA's potential as a best-in-class therapy for the treatment of patients with [relapsed/refractory multiple myeloma] given the totality of data to date across our studies.”

The investigational modified CAR T-cell therapy CART-ddBCMA is designed to make use of a novel BCMA-targeting binding domain for the management of relapsed/refractory multiple myeloma.

In the open-label phase 2 iMMagine-1 trial, an estimated population of 110 patients were intended to receive a single dose of CART-ddBCMA at 115±10⁶ CAR-positive cells via intravenous infusion.

The study’s primary end point is overall response rate (ORR) as assessed by an independent review committee based on International Myeloma Working Group criteria. Secondary end points include stringent complete response (CR) or CR rate, investigator-assessed ORR, duration of response, very good partial response (PR) or PR rate, time to initial response, progression-free survival, overall survival, safety, pharmacokinetics, and health-related quality of life.

Those 18 years and older who have received at least 3 prior lines of systemic therapy including a proteasome inhibitor, immunomodulatory drug, and an anti-CD38 antibody are eligible for enrollment on the trial. Patients are also able to enroll if they have documented measurable disease, an ECOG performance status of 0 to 1, a life expectancy of more than 12 weeks, adequate organ function, and recovery from any AEs resulting from prior systemic anti-cancer therapy, radiotherapy, or surgery.

Patients with solitary plasmacytomas without evidence of other measurable disease or a history of allergy or hypersensitivity to components of CART-ddBCMA are unable to enroll on the trial.

According to a prior readout of data from a phase 1 expansion trial (NCT04155749) assessing CART-ddBCMA as a treatment for 38 evaluable patients with relapsed/refractory multiple myeloma in December 2022, the experimental treatment produced an ORR of 100%.3 Additionally, investigators identified no tissue-targeted toxicities and 1 event of grade 3 immune effector-associated neurotoxicity syndrome.

“We look forward to presenting data from our phase 1 study later [in 2023] as well as preliminary data from the iMMagine-1 study in the second half of 2024,” Elghandour concluded.¹

References

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 16, 2023. https://shorturl.at/lpCFL
2. Arcellx announces clinical hold for its IMMagine-1 phase 2 clinical program. News release. Arcellx, Inc. June 19, 2023. Accessed August 16, 2023. bit.ly/3NCXBKz
3. 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 16, 2023. https://bit.ly/3Jj4fDp