FDA Puts on Hold Phase 1 Cellectis Trial Testing CAR T-cell Therapy UCARTCS1A

A Phase 1 trial assessing Cellectis’ investigational CAR T-cell therapy, UCARTCS1A, for the treatment of relapsed or refractory multiple myeloma has been placed on hold by the U.S. Food and Drug Administration (FDA), the company announced in a press release.

The MELANI-01 study (NCT04142619) was assessing the safety and clinical activity of different doses of UCARTCS1A, administered in a single infusion, with the aim of determining the optimal dose for further testing.

The clinical hold came after one patient, who received the second dose level of the therapy, died from cardiac arrest during the study.

Before enrolling in the MELANI-01 study, the patient had previously been treated, without success, with several lines of treatment, including other forms of CAR T-cell therapy. Investigators are now gathering information to determine whether the cardiac arrest occurred as a direct result of treatment with UCARTCS1A.

Cellectis is working closely with the FDA to lift this clinical hold, which will require the company to make changes to the study’s protocol to enhance participants’ safety. The company stated that it plans to submit a formal proposal with the amended trial protocol, along with additional information, to the FDA as soon as possible.

Before the FDA announced the clinical hold on MELANI-01, Cellectis already had been planning to enroll more patients into the first dose group — which seemed to be the best dose to be used in future studies, based on a preliminary analysis. For this reason, the company had already started updating the study’s protocol to reflect these changes.

“We share the FDA’s commitment to patient safety and are working collaboratively with the agency and the investigators to resolve this clinical hold,” said Carrie Brownstein, MD, chief medical officer of Cellectis.

“The safety of patients enrolled in our clinical trials is our utmost priority and we at Cellectis remain committed to safely resuming the clinical development of UCART product candidate targeting CS1 for patients with multiple myeloma and unmet medical need,” Brownstein added.

Chimeric antigen receptor T-cell therapy, more commonly known as CAR T-cell therapy, is a type of immunotherapy in which T-cells — a type of immune cell in the body with anti-cancer activity — are collected and genetically modified to better recognize and eliminate cancer cells. The engineered cells are expanded in the laboratory, then infused into the patient to fight cancer.

UCARTCS1A contains T-cells engineered to produce a man-made chimeric antigen receptor, or CAR, that helps to recognize and kill cells containing the protein CS1 while leaving healthy cells unharmed. CS1, also known as SLAMF7, is a protein found at high levels on the surface of myeloma cells.

Notably, UCARTCS1A is an allogeneic form of CAR T-cell therapy that uses T-cells from healthy donors, rather than those taken from patients. That means it can potentially be used as an off-the-shelf treatment.

Cellectis is developing two other allogeneic CAR T-cell therapy candidates for different types of blood cancers: UCART123 for acute myeloid leukemia; and UCART22 for relapsed or refractory B-cell acute lymphoblastic leukemia.

Both therapies are being tested in dose-escalation Phase 1 trials — AMELI-01 (NCT03190278) for UCART123 and BALLI-01 (NCT04150497) for UCART22 — that are enrolling patients in the U.S.