FDA Lifts Hold on Cellectis’ Phase I MELANI-01 Trial After Key Safety Adjustments

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The U.S. Food and Drug Administration (FDA) has lifted a clinical hold on Cellectis’ Phase I MELANI-01 trial evaluating multiple myeloma candidate UCARTCS1 just months after working with the French biopharmaceutical company to adjust its trial protocol to enhance patient safety.

UCARETCS1, an allogeneic, off-the-shelf, gene-edited T-cell therapy, was developed by Cellectis to treat CS1/SLAMF7-expressing hematologic cancers. The open-label, first-in-human, Phase I dose-escalation trial MELANI-01 is investigating UCARTCS1 specifically for the treatment of relapsed or refractory multiple myeloma. According to The American Cancer Society, an estimated 32,270 new cases of multiple myeloma will be diagnosed in 2020, and 12,830 deaths from the disease are also expected, indicating there exists a significant unmet treatment for this patient population.

A patient death in the trial led the FDA to place the clinical hold in July, telling Cellectis it needed to change the study’s protocol to address serious safety concerns. The patient who died in the trial had been treated with several lines of therapy prior to enrollment and subsequently developed fatal treatment-emergent cardiac arrest while participating in the study.

Before it was halted, the MELANI-01 trial had sites in Texas, New York and New Jersey. Cellectis had plans to expand enrollment at dose-level one, the level of which the company said may be the appropriate dose in the expansion cohort and the recommended dose for a future Phase II trial.

Cellectis, a 21-year-old biopharmaceutical company, is partnered with Arie Belldegrun’s Allogene. In 2018, the two companies announced they would continue their strategic cancer immunotherapy collaboration to develop off-the-shelf CAR-T cancer drugs.

The FDA previously paused a Cellectis trial in 2017, when another patient death led the agency to pause study into UCART123, a gene-edited T-cell investigational drug targeting CD123 for relapsed/refractory acute myeloid leukemia.

Paris-based Cellectis has not disclosed what changes it has made to its protocol; however, some analysts believe the company will closely monitor cytokine levels in patients. Additionally, the company may switch out a chemotherapy drug for a less-toxic alternative and/or exclude the enrollment of additional patients who have previously taken an investigational multiple myeloma CAR-T.

As the hold is lifted, Cellectis is continuing to work with its clinical site staff and investigators to obtain necessary local approvals to resume the trial and patient enrollment. Two other proprietary Phase I dose-escalation trials sponsored by Cellectis are currently enrolling participants. These trials include AMELI-01 evaluating UCART123 in relapsed and refractory acute myeloid leukemia and BALLI-01 evaluating UCART22 in relapsed and refractory B-cell acute lymphoblastic leukemia.

Cellectis’ Chief Medical Officer Carrie Brownstein, MD, was appointed to her role at the company in April, just as the company began to advance UCAR product pipeline in clinical trials.

“We remain confident in the potential clinical benefit of UCARTCS1 product candidate for patients with relapsed/refractory multiple myeloma, a widely unmet medical need that Cellectis will continue to address,” said Dr. Brownstein, in a statement. “The safety of patients enrolled in our clinical trials remains our priority, and we are committed to resuming the clinical development of this promising program.”

Following the news of the clinical hold lift, Cellectis’ stock rose 5.6% from $19.70 to $20.80.

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