BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial.

In this phase 2b randomized, controlled, double-blindtrial, we evaluated Descartes-08, an autologous BCMA-directed mRNA chimeric antigen receptor T cell therapy, in patients with generalized MG (gMG).

在这项2b期随机、对照、双盲试验中，我们评估了Descartes-08，一种针对BCMA的自体mRNA嵌合抗原受体T细胞疗法，在患有全身性重症肌无力（gMG）的患者中的效果。

Patients (n = 26) were randomly allocated to receive once-weekly intravenous infusions of Descartes-08 (n = 15) or placebo (n = 11) over 6 weeks.

患者（n = 26）被随机分配接受Descartes-08（n = 15）或安慰剂（n = 11）的每周一次静脉输注，持续6周。

The primary endpoint was a ≥5-point improvement in the MG Composite (MGC) score at month 3.

主要终点是第3个月时改良肌病复合评分（MG Composite, MGC）提高≥5分。

Secondary endpoints included the mean change from baseline in MGC, MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores by month 12.

次要终点包括在12个月内从基线开始的平均MGC、MG日常生活活动（MG-ADL）和定量肌无力（QMG）评分的变化。

At month 3, the proportion of patients achieving a ≥5-point improvement in the MGC score was significantly higher for those treated with Descartes-08 compared to placebo in the overall population (66.7% (n = 10/15) versus 27.3% (n = 3/11), P = 0.0472) and in a subpopulation of those positive for autoantibodies to the acetylcholine receptor (63.6% (n = 7/11) versus 12.5% (n = 1/8), P = 0.0258).

在第3个月，接受Descartes-08治疗的患者中，达到MGC评分提高≥5分的比例在整个人群中显著高于安慰剂组（66.7%（n = 10/15）对比27.3%（n = 3/11），P = 0.0472），并且在对乙酰胆碱受体自身抗体呈阳性的亚组人群中也显著高于安慰剂组（63.6%（n = 7/11）对比12.5%（n = 1/8），P = 0.0258）。

For patients treated with Descartes-08, the changes from baseline in mean MGC, MG-ADL and QMG scores at month 4 were -7.1, -5.5 and -4.8, respectively, with 83.0% of patients achieving a sustained and clinically meaningful response at month 12.

接受Descartes-08治疗的患者，在第4个月时，平均MGC、MG-ADL和QMG评分的基线变化分别为-7.1、-5.5和-4.8，其中83.0%的患者在第12个月实现了持续且具有临床意义的反应。

Notably, 33.0% of patients achieved minimum symptom expression (MSE) (MG-ADL score ≤1) by month 6, which was sustained through month 12.

值得注意的是，到第6个月时，有33.0%的患者实现了最小症状表达（MSE）（MG-ADL评分为1或以下），这一状态持续至第12个月。

Among biologic-naive patients, 55.60% achieved MSE by month 6, which was maintained through month 12 without additional treatment.

在生物制剂未经治疗的患者中，55.60%的患者在6个月内实现了MSE，并且在没有额外治疗的情况下，这一状态维持到了12个月。

Descartes-08 was generally safe and well tolerated.

Descartes-08通常被认为是安全且耐受性良好的。

Infusion-related reactions were the most common adverse events reported (Descartes-08, 80.0% (n = 16/20); placebo, 56.3% (n = 9/16)).

输液相关反应是最常见的不良事件报告（Descartes-08，80.0%（n = 16/20）；安慰剂，56.3%（n = 9/16））。

In summary, a single course of six once-weekly infusions of Descartes-08 was well tolerated and resulted in sustained clinically meaningful responses among patients with gMG.

总之，Descartes-08单次疗程六次每周一次的输液治疗耐受性良好，并在患有gMG的患者中产生了持续的临床意义反应。

ClinicalTrials.gov identifier: NCT04146051 .

临床试验注册号：NCT04146051。