FDA Lifts Hold on Phase 1 Trial for Car-T-Cell Therapy UCARTCS1A

The U.S. Food and Drug Administration (FDA) has lifted the clinical hold placed on a Phase 1 trial assessing Cellectis’ investigational CAR T-cell therapy, UCARTCS1A, for the treatment of relapsed or refractory multiple myeloma.

In September, the FDA placed a hold on the MELANI-01 trial (NCT04142619) based on safety concerns, after a patient who received the second lowest dose of the therapy died from cardiac arrest.

Since then, Cellectis has been working closely with the regulatory agency to address its requests, and has amended the MELANI-01 clinical protocol to increase patient safety. The company is now working with clinical staff and investigators to reopen the trial and restart enrollment.

“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,” Carrie Brownstein, MD, chief medical officer at Cellectis, said in a press release.

“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,” Brownstein added.

UCARTCS1A is a form of chimeric antigen receptor T-cell therapy, or CAR T-cell therapy, in which T-cells — a type of immune cell — are collected from healthy donors and engineered in a way that increases their ability to target and eliminate cancer cells.

Using cells from donors rather than patients means this therapy may be available as an “off-the-shelf” product, bypassing the long waiting times while the treatment is manufactured.

UCARTCS1 cells are modified to carry a man-made receptor targeting the SLAMF7, or CS1 protein, which is found at high levels on the surface of myeloma cells. The engineered cells are expanded in the laboratory, then infused into the patient to help fight the cancer.

MELANI-01 is assessing the safety and efficacy of UCARTCS1A in patients with relapsed or refractory multiple myeloma. The aim is to evaluate the clinical activity of different doses of UCARTCS1A, administered in a single infusion, and to determine the optimal dose to be used in future studies.

The trial intends to enroll a total of 18 participants (ages 18–64) at three sites in the U.S.: MD Anderson Cancer Center, Texas; Hackensack Meridian Health, New Jersey; and Weill Cornell Medicine, New York. More information on contacts and locations is available here.

To be eligible for the study, patients must have a confirmed diagnosis of active multiple myeloma and have relapsed after prior treatment.

Cellectis is recruiting patients in two other Phase 1 trials of CAR T-cell therapies. The AMELI-01 study (NCT03190278) is evaluating UCART123 for acute myeloid leukemia, while BALLI-01 (NCT04150497) is investigating UCART22 as a treatment for relapsed or refractory B-cell acute lymphoblastic leukemia.