1528 A phase I study of a novel BCMA×CD3 bispecific antibody EMB06 in relapsed or refractory multiple myeloma

医学 细胞因子释放综合征 耐受性 多发性骨髓瘤 耐火材料(行星科学) 内科学 药效学 肿瘤科 抗体 药代动力学 免疫疗法 不利影响 免疫学 癌症 天体生物学 物理 嵌合抗原受体
作者
Peter Tan,Sorab Jehangir Shavaksha,H. Miles Prince,Qingsong Yin,Chunrui Li,Zhen Cai,Bao Li,Hongyan Jing,Peilong Lai,Qiumei Deng,Mingfei Zhang,Shuqi Zeng,Qiaoyang Lu,Chengjun Jiang,Fang Ren,Danqing Wu,Jian‐Qing Mi
标识
DOI:10.1136/jitc-2023-sitc2023.1528
摘要

Background

Despite recent advances in T-cell engager based multiple myeloma therapies, high rate of cytokine release syndrome (CRS) and severe neurotoxicity remains a challenge in clinic. EMB-06 is a novel 2+2 BCMA×CD3 T-Cell engaging bispecific antibody developed based on the EpimAb’s proprietary Fabs-In-Tandem-Immunoglobulin (FIT-Ig®) platform. Differentiated from existing T-cell engagers, EMB-06 comprises tetravalent binding domains in cis-configuration and proprietary anti-CD3 arms with optimized affinity. It induced modest levels of cytokine release yet retained robust anti-tumor activity in preclinical studies. Here we report the initial results from an ongoing multicenter, first-in-human, Phase I study of EMB-06 in relapsed or refractory multiple myeloma (RRMM).

Methods

The Phase I study evaluates escalating doses of once weekly IV administrations of EMB-06 in patients (pts) with RRMM who have failed or are intolerant to standard therapies. Dose escalation was guided by the Bayesian optimal interval (BOIN) design. Primary objectives were to assess safety, tolerability, and determine the MTD and/or RP2Ds. Secondary objectives were to assess pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary anti-tumor activities.

Results

As of Aug 28, 2023, 33 pts had been treated with EMB-06 at 0.2mg to 200mg. Median age was 66 y (46–82). Median prior lines of therapies were 3 (2–6) and 26 (79%) pts were refractory to the most recent line of therapy. Treatment-related AEs (TRAEs) were reported in 20 (61%) pts, with Gr ≥3 occurring in 7 (21%) pts. The most common TRAEs include ALT increase (18%), leukopenia (18%), ALP increase (15%), neutropenia (15%), anemia (12%), AST increase (12%), GGT increase (12%), lymphopenia (12%) and CRS (12%). All CRS were Grade 1. Only 1 patient experienced treatment related neurotoxicity (Gr.1 paresthesia). One DLT (pneumonia, cardiac failure, creatinine increased and hepatic insufficiency) was observed at 60mg cohort. EMB-06 shows dose proportional increase in PK exposure across 0.2–120 mg, and the median half-life after single dosing is 4.4 days. PD activity (T cell redistribution and activation along with transient release of low-level cytokines) was observed at doses ≥0.6mg. The ORR was 29% (9/31) among 31 response evaluable pts. Of the 5 evaluable pts treated with doses ≥120mg, the ORR was 100% (1 CR, 2 VGPR, 2 PR).

Conclusions

EMB-06 demonstrated a differentiated safety profile in RRMM pts with exceptionally low CRS and neurotoxicity rates so far. An initial ORR of 100% has been observed at doses ≥120mg. Updated data will be shared at the meeting.

Trial Registration

The clinical trial was registered with www.clinicaltrials.gov (NCT04735575).

Ethics Approval

The trial was done according to Good Clinical Practice and the Declaration of Helsinki. The protocol and amendments were approved by the institutional review board or ethics committee at each site. And all participants gave informed consent before taking part in the trial. The name of the ethics committee(s) or institutional review board(s), the number/ID of the approval(s) are as follow: Epworth health – No. 2020-12-1350 Sunshine Coast Haematology and Oncology Clinic- No. 2020-12-1350-AA One Clinical Research - No. 2020-12-1350-AB Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiaotong University School Of Medicine-No. 2021-73 Henan Cancer Hospital Medical Science Research Ethics Committee-No. 2021-381-002 Clinical Trial Ethics Committee of Huazhong University of Science and Technology-No. 2021-218 Ethics Committee of the First Affiliated Hospital, School Of Medicine, Zhejiang University-No. 2021-627 Ethics Committee of Beijing Jishuitan Hospital-No. 20210902-01 Peking University Third Hospital Medical Science Research Ethics Committee-No.2022-220-02 Ethics Committee of Guangdong Provincial People’s Hospital-No. YW2023-011-02

Consent

Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
木木完成签到,获得积分20
1秒前
小岚花发布了新的文献求助10
1秒前
cindywu关注了科研通微信公众号
2秒前
蔡翌文发布了新的文献求助10
2秒前
scabbard24发布了新的文献求助10
2秒前
orixero应助大大的西瓜采纳,获得10
3秒前
3秒前
4秒前
weijie完成签到,获得积分10
4秒前
爆米花应助obdixp采纳,获得20
5秒前
5秒前
小王发布了新的文献求助10
6秒前
8秒前
可靠的如之完成签到,获得积分10
9秒前
专注棒棒糖完成签到 ,获得积分10
9秒前
9秒前
Lily发布了新的文献求助10
9秒前
10秒前
YZQ发布了新的文献求助10
11秒前
黑咖啡完成签到,获得积分10
11秒前
Liufgui应助可靠的如之采纳,获得10
13秒前
科研通AI2S应助阿俊采纳,获得10
14秒前
15秒前
17秒前
19秒前
19秒前
JamesPei应助YZQ采纳,获得10
20秒前
Orange应助邪恶花生米采纳,获得10
20秒前
weijie发布了新的文献求助10
20秒前
hf完成签到,获得积分10
20秒前
20秒前
22秒前
量子星尘发布了新的文献求助30
23秒前
硅负极完成签到,获得积分10
23秒前
zzt发布了新的文献求助10
23秒前
24秒前
Dr.Yang发布了新的文献求助10
25秒前
27秒前
刻苦的秋柔完成签到,获得积分10
29秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988920
求助须知:如何正确求助?哪些是违规求助? 3531290
关于积分的说明 11253247
捐赠科研通 3269903
什么是DOI,文献DOI怎么找? 1804830
邀请新用户注册赠送积分活动 882027
科研通“疑难数据库(出版商)”最低求助积分说明 809052