CAR T-cell therapy anito-cel set for Phase 3 trial in multiple myeloma

Global study in adults with advanced disease expected to open this year

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Arcellx and Kite Pharma are planning to launch a Phase 3 clinical trial, dubbed iMMagine-3, to test their cell therapy anitocabtagene autoleucel (anito-cel) in people with hard-to-treat multiple myeloma.

“We are pleased to start the Phase 3 pivotal trial, iMMagine-3, in the second half of this year given the tremendous unmet need that remains in patients with relapsed and/or refractory multiple myeloma,” Cindy Perettie, executive vice president of Kite, said in a press release from both companies, which are co-developing anito-cel.

iMMagine-3 aims to enroll up to 450 adults with relapsed and/or refractory multiple myeloma (RRMM) who have received one to three previous lines of treatment, including an immunomodulatory agent and a CD38 inhibitor. It is expected to involve about 130 sites across North America, Europe, and other regions.

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Trial in multiple myeloma patients with up to three previous treatment lines

“Our global iMMagine-3 trial will evaluate anito-cel as a second through fourth line treatment in patients with multiple myeloma who were previously exposed to both an immunomodulatory drug and an anti-CD38 monoclonal antibody,” said Rami Elghandour, Arcellx’s chairman and CEO.

According to Elghandour, this group of patients “represents an emerging significant unmet clinical need,” and selecting this group for the Phase 3 trial “allows us to maximize the impact of anito-cel as it captures what will become the largest second line patient population based on the current treatment paradigm, as anti-CD38 therapies move to front line treatment.”

Anito-cel, formerly known as CART-ddBCMA, is a CAR T-cell therapy. In this type of treatment, immune cells called T-cells are collected from a patient, then engineered in a lab to equip them with a human-made molecular receptor called a chimeric antigen receptor or CAR.

In antio-cel, the engineered T-cells specifically are equipped with a CAR that targets BCMA, a protein highly produced by myeloma cells. The modified T-cells then are infused to the patient, and the CAR directs them to attack and destroy BCMA-positive myeloma cells.

In the Phase 3 iMMagine-3 trial, participants will be randomly assigned to either a single infusion of anito-cel, or their doctor’s choice of standard-of-care myeloma treatments.

Those assigned to the CAR T-cell therapy first will be given a three-day regimen of chemotherapies (fludarabine plus cyclophosphamide) that aims to eliminate the patient’s existing immune cells, making room for the modified T-cells.

The trial’s main goal is to compare progression-free survival, or the time patients are alive without their cancer growing or worsening, between the two groups. The study also will compare response rates, minimal residual disease negativity, overall survival, and safety. Minimal residual disease refers to the small number of myeloma cells that can remain after treatment and cause a relapse.

Interim findings in a Phase 2 trial of anito-cel expected this year

Kite’s facility in Maryland will be manufacturing anito-cel for the study, which “will enable broader and earlier patient access to anito-cel,” Elghandour said.

“As we prepare for this pivotal program, we look forward to leveraging our manufacturing expertise to further position anito-cel as a potential best-in-class cell therapy,” Perettie said. “We know manufacturing quality, reliability and speed are critically important.”

While the Phase 3 trial is in the works, the Phase 2 iMMagine-1 trial (NCT05396885) is ongoing. That trial is testing anito-cel in up to 110 adults with RRMM who’ve had least three previous therapy lines, including an immunomodulatory agent, a CD38 inhibitor, and a proteasome inhibitor. This group is said to be triple-class exposed.

Patient enrollment is ongoing at 20 sites across the U.S. The iMMagine-1 trial was put on partial hold by the U.S. Food and Drug Administration last year after one participant died, but the hold was lifted a couple of months later with trial modifications meant to prevent and manage the risk of adverse events.

This study’s main goal is to assess how many patients respond to the cell therapy after two years. Preliminary results are expected by year’s end, the release stated.

Interim data from 38 triple-class exposed RRMM patients in an ongoing Phase 1 trial (NCT04155749) showed that all responded to anito-cel, with about three-quarters achieving a complete response.