Cellectis通用型MM CAR-T临床叫停

有人说是因为CS1/SAMLF7在心脏表达，但是查了一下也一般，所以也不好先扣帽子，就像CD19 CAR T里面也报道有心脏骤停，但CD19的确不在心脏表达一样

Cellectis Reports Clinical Hold Placed on MELANI-01 Study

July 6, 2020 – New York (N.Y.) – Celletics(Euronext Growth: ALCLS - Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (基因编辑的同种异体CAR-T细胞，UCART), today announced that the MELANI-01 trial has been placed on clinical hold by the U.S. Food and Drug Administration (被FDA叫停).

此次叫停影响UCARTCS1A，用于治疗表达CS1/SLAMF7的恶性血液瘤，叫停原因是一例r/r MM患者在接受该疗法第2剂量(DL2)的治疗后死亡。该患者先前已接受过包括自体CAR-T在内的多轮治疗后失败，在接受了UCARTCS1A治疗后，死于心脏骤停的TEAE。

This clinical hold which impacts one of the three Cellectis product candidates currently in clinical studies, was initiated following the submission of a safety report regarding one patient enrolled in the MELANI-01 study at dose level two (DL2), with relapsed and refractory multiple myeloma. This patient, who had been treated unsuccessfully, prior to enrollment with numerous lines of prior therapy, including autologous CAR T-cells, experienced a fatal treatment-emergent adverse event of cardiac arrest. Clinical evaluation of the case remains ongoing and additional details as to the immediate and underlying causes of this event are being collected.

在FDA叫停前，Cellectis已经决定扩大第一剂量(DL1)的患者，基于临床及转化结果看这可能就是适合在扩张阶段进一步评估并可能是作为RP2D。此外，由于UCARTCS1A的新颖作用机制，该公司已开始监测并减轻额外的潜在风险。考虑到新颖的机制，公司已经开始更新临床方案，监测并减轻额外的潜在风险。

Of note, prior to the clinical hold being issued by the FDA, Cellectis had decided to expand enrollment at DL1, which may be the appropriate dose for further evaluation in the expansion portion of the trial and potentially the recommended Phase 2 dose based on an assessment of the preliminary clinical and translational data. The Company had begun executing updates to the clinical protocol to reflect this as well as to monitor and mitigate for additional potential risks given its novel mechanism of action.

“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, 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.”

Cellectis正与FDA密切合作以满足安全要求，包括修改MELANI-01临床方案来增强安全性，并希望合适的时候提交包括修改后的方案在内的要求的信息。

Cellectis is working closely with the FDA to address the agency’s requests including changes to the MELANI-01 clinical protocol designed to enhance patient safety, and expect to submit requested information including an amended protocol in due course.

另两个Ph1剂量递增的患者入组仍在继续：AMELI-01（评估UCART123治疗r/r AML）和BALLI-01 （评估UCART22治疗r/r B-ALL）

Patient enrollment is ongoing in our two other proprietary Phase 1 dose escalation trials: 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.

About MELANI-01

MELANI-01 is a Phase 1 open-label First-In-Human dose escalation clinical study evaluating UCARTCS1A product candidate for the treatment of patients with relapsed or refractory multiple myeloma (MM). UCARTCS1A is an allogeneic, off-the-shelf, gene-edited T-cell product candidate designed for the treatment of CS1/SLAMF7-expressing hematologic malignancies. CS1 (SLAMF7) is highly expressed on MM tumor cells.

About Multiple Myeloma (MM)

Multiple myeloma is a cancer that affects a type of white blood cells called plasma cells that are specialized mature B-cells, which secrete antibodies to combat infections. Multiple myeloma is characterized by the uncontrolled proliferation of neoplastic plasma cells in the bone marrow, where they overcrowd healthy blood cells. Although MM is a chronic disease and an exact cause has not yet been identified, researchers have made significant progress over the years in managing the disease through better understanding MM’s pathophysiology. The progress in finding a cure needs to be continued as The American Cancer Society estimates that 32,110 new cases of MM will be diagnosed, and 12,960 deaths are expected to occur in 2019 in the U.S. alone.