更新于：2024-06-24

OriCAR-017

靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）

更新于：2024-06-24

概要

概要

基本信息

药物类型

自体CAR-T

别名

anti-GPCR5D CAR T-cell therapy(Origincell Therapeutics)、Chimeric antigen receptor (CAR)-T cell therapy targeting G protein-coupled receptor class-C group-5 member-D (GPRC5D).、GPRC5D-CAR-T

+ [2]

靶点

GPRC5D

作用机制

GPRC5D抑制剂(G蛋白偶联受体家族C组5成员D抑制剂)、免疫细胞毒性、T淋巴细胞替代物

治疗领域

肿瘤免疫系统疾病心血管疾病+ [1]

在研适应症

多发性骨髓瘤

非在研适应症-

原研机构

原启生物科技（上海）有限责任公司

在研机构

原启生物科技（上海）有限责任公司

非在研机构-

最高研发阶段临床1/2期

首次获批日期-

最高研发阶段(中国)临床1/2期

特殊审评孤儿药 (美国)

关联

项与靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）相关的临床试验

NCT06271252 / Recruiting临床1期

A Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Anti-GPRC5D CAR-T Cell Product (OriCAR-017) in Subjects With Relapsed/Refractory Multiple Myeloma.

The is a first clinical study for Oricell Therapeutics Inc. in the United States to evaluate the safety, PK, PD and preliminary efficacy of our anti-GPRC5D cell product (OriCAR-017) in subjects with relapsed/refractory multiple myeloma.
RIGEL Study

开始日期2024-04-03

申办/合作机构

原启生物科技（上海）有限责任公司

CTR20232814 / Recruiting临床1/2期

一项在复发难治多发性骨髓瘤受试者中评估OriCAR-017安全性、药代动力学和有效性的开放性、多中心临床研究（MERCURY）

I期主要目的评估OriCAR-017治疗复发难治多发性骨髓瘤的安全性、耐受性和剂量限制性毒性；II期主要目的评估OriCAR-017治疗治疗复发难治多发性骨髓瘤的临床有效性

开始日期2023-11-28

申办/合作机构

原启生物科技（上海）有限责任公司

NCT06182696 / Recruiting临床1/2期

An Open Label,Multi-center Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Autologous T Cell Injection Targeting GPRC5D OriCAR-017 in Patients With Relapsed and/or Refractory Multiplemyeloma

An open label, dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of OriCAR-017 in R/RMM

开始日期2023-10-26

申办/合作机构

原启生物科技（上海）有限责任公司

100 项与靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）相关的临床结果

登录后查看更多信息

100 项与靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）相关的转化医学

登录后查看更多信息

100 项与靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）相关的专利（医药）

登录后查看更多信息

项与靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）相关的文献（医药）

Blood cancer journal

GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review

Review

作者: Bahlis, Nizar ; Vishwamitra, Deeksha ; Heuck, Christoph ; Hilder, Brandi ; van de Donk, Niels W C J ; Tolbert, Jaszianne ; Cornax, Ingrid ; Kane, Colleen ; Rodriguez-Otero, Paula ; Masterson, Tara ; Pillarisetti, Kodandaram ; Chari, Ajai ; Gray, Kathleen ; Moreau, Philippe ; Renaud, Thomas ; Verona, Raluca

Abstract:

Multiple myeloma is a genetically complex and heterogenous malignancy with a 5-year survival rate of approximately 60%. Despite advances in therapy, patients experience cycles of remission and relapse, with each successive line of therapy associated with poorer outcomes; therefore, therapies with different mechanisms of action against new myeloma antigens are needed. G protein–coupled receptor class C group 5 member D (GPRC5D) has emerged as a novel therapeutic target for the treatment of multiple myeloma. We review the biology and target validation of GPRC5D, and clinical data from early phase trials of GPRC5D-targeting bispecific antibodies, talquetamab and forimtamig, and chimeric antigen receptor T cell (CAR-T) therapies, MCARH109, OriCAR-017, and BMS-986393. In addition to adverse events (AEs) associated with T-cell–redirection therapies irrespective of target, a consistent pattern of dermatologic and oral AEs has been reported across several trials of GPRC5D-targeting bispecific antibodies, as well as rare cerebellar events with CAR-T therapy. Additional studies are needed to understand the underlying mechanisms involved in the development of skin- and oral-related toxicities. We review the strategies that have been used to manage these GPRC5D-related toxicities. Preliminary efficacy data showed overall response rates for GPRC5D-targeting T-cell–redirecting therapies were ≥64%; most responders achieved a very good partial response or better. Pharmacokinetics/pharmacodynamics showed that these therapies led to cytokine release and T-cell activation. In conclusion, results from early phase trials of GPRC5D-targeting T-cell–redirecting agents have shown promising efficacy and manageable safety profiles, including lower infection rates compared with B-cell maturation antigen- and Fc receptor-like protein 5-targeting bispecific antibodies. Further clinical trials, including those investigating GPRC5D-targeting T-cell–redirecting agents in combination with other anti-myeloma therapies and with different treatment modalities, may help to elucidate the future optimal treatment regimen and sequence for patients with multiple myeloma and improve survival outcomes.

2023-02-01·The Lancet. Haematology

GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial

Article

作者: Cui, Jiazhen ; Zhou, Jincai ; Fu, Shan ; Hu, Yongxian ; Wang, Dongrui ; Huang, He ; Zhang, Mingming ; He, Xiaowen Peter ; Huang, Simao ; Chen, Siye ; Zhou, Linghui ; Zhang, Wei ; Tang, Yu ; Zhou, Xinkai ; Wei, Guoqing ; Ding, Xiaomin ; Luo, Xueping ; Kuang, Jiao

BACKGROUND:

Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) has shown activity in treating relapsed or refractory multiple myeloma; however, relapse is still common, and new targets are needed. We aimed to assess the activity and safety profile of G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma.

METHODS:

POLARIS was a first-in-human, single-centre, single-arm, phase 1 trial of GPRC5D-targeted CAR T cells (OriCAR-017) done at the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. Eligible patients were adults aged 18-75 years with a diagnosis of relapsed or refractory multiple myeloma and an ECOG performance status of 0-2, had GPRC5D expression in bone marrow plasma cells greater than 20% or were positive for GPRC5D by immunohistochemistry, and had received at least three previous lines of treatment including proteasome inhibitors, immunomodulatory drugs, and chemotherapy. Patients were consecutively assigned to receive a single dose of intravenous OriCAR-017 at 1 × 10⁶ CAR T cells per kg, 3 × 10⁶ CAR T cells per kg, or 6 × 10⁶ CAR T cells per kg in the dose-escalation phase. In the expansion phase, patients received the recommended phase 2 dose. Recruitment to the expansion phase terminated early due to the COVID-19 pandemic on May 1, 2022. The primary endpoints were safety, the maximum tolerated dose and the recommended phase 2 dose. Safety and activity analyses included all patients who received OriCAR-017. This trial is registered with ClinicalTrials.gov, NCT05016778. This trial has been completed and is entering long-term follow-up.

FINDINGS:

Between June 9, 2021, and Feb 28, 2022, we recruited 13 patients for inclusion into the study. One patient was excluded because of GPRC5D negativity and two patients discontinued after apheresis because of rapid progression. Nine patients were assigned to the dose escalation phase (three received 1 × 10⁶ CAR T cells per kg, three received 3 × 10⁶ CAR T cells per kg, and three received 6 × 10⁶ CAR T cells per kg). The maximum tolerated dose was not identified, because no dose-limiting toxic effects were observed. On the basis of safety and preliminary activity, the recommended phase 2 dose was set at 3 × 10⁶ CAR T cells per kg, which was received by one additional patient in the dose expansion phase. Five patients (50%) were female, five (50%) were male, and all were Chinese. Five patients (50%) were previously treated with BCMA-targeted CAR T-cell therapy. Median follow-up was 238 days (IQR 182-307). There were no serious adverse events and no treatment-related deaths. The most common grade 3 or worse adverse events were haematological, including neutropenia (ten [100%] of ten patients), thrombocytopenia (nine [90%]), leukopenia (nine [90%]), and anaemia (seven [70%]). All patients had cytokine release syndrome (nine [90%] grade 1 and one [10%] grade 2). No neurological toxic effects were reported. Ten (100%) of ten patients had an overall response, of whom six (60%) had a stringent complete response and four (40%) had very good partial response. Two patients discontinued due to disease progression (one GPRC5D-positive patient in the middle-dose group and one GPRC5D-negative patient in the low-dose group).

INTERPRETATION:

The results of this study suggest that GPRC5D is an active target for immunotherapy in multiple myeloma. GPRC5D-targeted CAR T-cell therapy is a promising treatment modality for patients with relapsed or refractory multiple myeloma and deserves further testing.

FUNDING:

OriCell Therapeutics.

项与靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）相关的新闻（医药）

2024-06-21

·今日头条

缓解率近100%！四款中国自研CAR-T疗法重击肠癌、胰腺癌、血液瘤

ASCO年会是全球最大的多学科肿瘤学会议，每年都有来自全球100多个国家的肿瘤学专家、学者参会，共同探讨当今各类恶性肿瘤治疗的前沿进展，因此也被亲切地誉为“ 肿瘤界的奥斯卡盛会 ”。今年美国临床肿瘤学会（ASCO）年会也如期而至，已于2024年5月31~6月4日期间，在美国芝加哥盛大召开。本次大会除了公布癌症新药治疗领域的最新研究成果外，还展示了各国在癌症免疫治疗领域取得的最新成就。其中，我国几款自研的CAR-T产品也惊艳亮相，为血液肿瘤及多款实体瘤患者带来了“一线生机”！同时也在世界舞台上，展示了我国在前沿抗癌研发领域的实力，下面全球肿瘤医生网医学部小编就简单盘点一下，以供大家参考。国研新型CAR-T疗法，多款血液肿瘤克星 PART1 CD7 CAR-T细胞：暴击血液肿瘤，患者获得完全缓解复发或难治性血液系统肿瘤患者的治疗选择有限且预后不良，5年总生存率不到20%。虽然异基因造血干细胞移植（HSCT）为治疗侵袭性血液系统癌症提供了一种关键策略，但HSCT治疗也可能出现移植物抗宿主病（GVHD）、条件相关毒性作用等不良反应，此外，部分健康状况不佳的患者也无法接受该治疗。因此，迫切需要寻求新的治疗方法，而CAR-T疗法的出现，为血液肿瘤患者带来了新的希望。世界知名期刊《新英格兰医学杂志》报道了一项关于“ CD7 CAR-T细胞，治疗复发或难治性CD7阳性血液肿瘤 ”的临床研究（NCT04599556）。 2021年11月~2023年9月期间，共入组10例复发或难治性CD7阳性癌症患者，其中包括7例急性骨髓系白血病（AML）、2例 T细胞急性淋巴细胞白血病（ALL）、1例 T细胞淋巴母细胞淋巴瘤（IVA级）。中位年龄为56.5岁（范围，13.7~72.5岁），所有患者均有骨髓受累表现，中位原始细胞百分比为36.0% （范围，2~87），原始细胞CD7表达的中位百分比为93.0% （范围，80.7~97.7），且既往均接受过大量治疗，中位疗程为9.5个疗程（范围，4~15个疗程）。入组后，先接受强化淋巴细胞清除方案（环磷酰胺、氟达拉滨、依托泊苷），之后接受 CD7 CAR-T细胞回输治疗。经过15.1个月的中位随访，结果显示： 1、完全缓解（CR）：所有患者（n=10）在接受CAR-T细胞治疗后，均获得完全缓解（CR）。但血液学恢复不完全，并有4级全血细胞减少症。截至2023年11月8日（数据截止日），6例患者未接受任何治疗，仍处于微小残留病灶（MRD）阴性完全缓解状态（详见下图）。 ▲图源“N Engl J Med”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 2、总生存率： 1年预估总生存率为68% [95% 置信区间（CI），43~100]，详见图a。 3、无病生存率： 1年预估无病生存率为54% （95% CI，29~100），详见图b。 ▲图源“N Engl J Med”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 PART2 OriCAR-017：复发/难治性多发性骨髓瘤的新希望，总缓解率可达100.0%！ OriCAR-017是一种新型靶向GPRC5D的嵌合抗原受体T细胞（CAR-T）疗法，其新药IND在获得中国国家食品药品监督管理局（NMPA）批准后，在 2024年1月又获得美国FDA的IND批准，为复发性/难治性多发性骨髓瘤（RR MM）患者，带来了新的治疗希望。 ▲截图源自“ASCO Publications” 2024美国临床肿瘤学会（ASCO）年会上，公布了“ OriCAR-017治疗复发/难治性多发性骨髓瘤（RR MM）1期临床试验 ”的长期随访结果。该研究共入组10例RR MM患者，位年龄为64岁（范围为41~71岁），截止至2024年1月16日，最后一名患者已完成了24个月的随访，结果显示： 1、在所有患者（n=10）中：其总缓解率（ORR）达到惊人的 100.0% ！严格完全缓解率（sCR）为80.0% 。中位无进展生存期（mPFS）为11.37个月（95%C1，5.93-18.00）。中位缓解持续时间（mDoR）为10.43个月（95%CI，5.00-17.00）。在治疗第28天，微小残留病灶阴性率（MRD）达到了100% ；且在第3个月时，进一步检测确认仍显示100%阴性。 2、在高剂量组中（67%为BCMA CAR-T经治患者）：中位无进展生存期（mPFS）为19.10个月（95%CI，8.30-NR），中位缓解持续时间（mDoR）为17.23个月（95%CI，7.33-NR）。综上，OriCAR-017对复发/难治性多发性骨髓瘤（RR MM），包括抗CD38、PIs、IMIDs难治且BCMA CAR-T治疗失败的患者，均表现出深入且持久的反应，且安全性良好。长期疗效及安全性随访结果表明，OriCAR-017有望成为RRMM患者的有效治疗选择！中国患者如何寻求CAR-T疗法帮助？目前正有多款CAR-T临床实验正在进行中，主要针对以下靶点及肿瘤类型： ① GUCY2C ：用于治疗结直肠癌； ② C3 ：用于治疗肝癌等； ③ PSMA ：用于治疗前列腺癌等； ④ Claudin18.2 ：用于治疗胃癌、胰腺癌等； ⑤ CEA ：用于治疗胰腺癌、胃癌、肺癌、乳腺癌、结肠癌等； ⑥ MUC-1 ：用于治疗肝癌、胰腺癌、肺癌、胃癌、结肠癌等； ⑦ GPEGFＲvII ：用于治疗神经胶质瘤、头颈部肿瘤等； ⑧ 间皮素（mesothelin）：用于治疗胰腺癌、肺癌、卵巢癌、间皮瘤等； ⑨ B7-H3 ：用于治疗尤文肉瘤、髓母细胞瘤、肾母细胞瘤、神经母细胞瘤、横纹肌肉瘤、特别难以治疗的脑干肿瘤（DIPG）等。做过基因检测的癌友，可自行查看检测报告，一旦发现存在上述突变，可提交至全球肿瘤医生网医学部初步评估是否有机会参加相关的临床试验。新型CAR-T疗法横空出世，剑指多款实体瘤 PART1 IM96：针对转移性结直肠癌，中位无进展生存期达7个月之久 IM96是一款靶向GUCY2C（鸟苷酸环化酶2C）的CAR-T疗法。其中，GUCY2C靶点在结直肠癌的所有阶段均有异位表达，且在肠道中受限。 ▲截图源自“ASCO Publications” 本次ASCO大会公布了“ IM96治疗转移性结直肠癌的I期临床研究（NCT05287165） ”结果。截至2023年12月，共有20例既往接受过≥3种疗法失败的患者入组，中位年龄为52.5岁，其中55%的患者存在肝转移，60.0%的患者发现 KRAS突变，15.0%的患者发现 BRAF突变，5.0%的患者发现 NRAS突变。入组后先接受氟达拉滨+环磷酰胺预处理；之后再接受 IM96单次回输治疗。并按照回输的细胞剂量不同，分为四组，即 DL1组（3×108）、 DL2组（6×108）、 DL3组（12×108）、 DL4组（20×108）。结果显示，在19例可评估疗效的患者中，疾病控制率（DCR）高达73.7% ，客观缓解率（ORR）达26.3% 。其中，DL3组患者的客观缓解率（ORR）达到40.0% ，中位无进展生存期（PFS）为7个月，中位反应持续时间为10个月。无反应患者在6个月内，均未出现疾病进展。肿瘤反应与所有患者的癌胚抗原水平显著下降相关。总之，上述结果显示， IM96在pMMR转移性结直肠癌（mCRC）患者中，具有持久的疗效和可接受的安全性，尤其在肝转移患者中显示出较高的治疗潜力。针对结直肠癌的CAR-T细胞治疗方法首先，获取、选择，并在体外激活人类T细胞。其次，进行基因改造，以诱导T细胞中的CAR表达，并扩增和配制获得CAR-T细胞，以制造具有相应质量控制的CAR-T细胞产品。最后，将CAR-T细胞产品施用于患者，预计通过靶向不同的结直肠癌（CRC）抗原，以精准识别并清除肿瘤细胞（详见下图）。 ▲图源“MDPI”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 PART2 CT041-CG4006：治疗胃肠道肿瘤1阶段结果，疾病控制率高达83.0%！ CT041是一款靶向claudin18.2（CLDN18.2）的嵌合抗原受体T（CAR-T）细胞候选产品，用于治疗Claudin18.2阳性实体瘤（如胃癌/食管胃结合部腺癌、胰腺癌）等。CLDN18.2在多种恶性肿瘤，尤其是胃肠道肿瘤中高表达，因而正在成为癌症治疗的新靶点。CT041于2020年，被美国食品药品监督管理局（FDA）授予“孤儿药”资格，用于胃癌/食管胃结合部腺癌的治疗；该产品又于2021年，被欧洲药品管理局（EMA）授予“孤儿药”资格，用于治疗晚期胃癌。 ▲截图源自“ASCO Publications” 在2024年ASCO大会上，公布了“ CT041-CG4006第1阶段试验（NCT03874897）的最终结果 ”。在2019年3月26日~2024年1月26日期间，共有98例患者入组接受CT041回输治疗，其中包括胃癌（n=73）、胰腺癌（n=10）、肠癌（n=8）、胆道癌（n=4）、其他肿瘤（n=3），中位随访期为29.7（范围：1.2，35.5）个月。结果显示如下： 1、在所有患者（N=98）中：其客观缓解率（ORR）为37.8%，疾病控制率（DCR）高达75.5% ，中位总生存期（OS）为8.4个月（95% CI：7.0,10.0），中位无进展生存期（PFS）为4.4个月（95% CI：4.0,6.0）。 2、在接受CT041单药治疗，且所有可评估疗效的胃癌（GC）患者（n=55）中：其中位总生存期（OS）为9.7个月（95%CI：7.1，14.4），中位无进展生存期（PFS）为5.8个月（95%CI：4.2，8.4）。其中，在可测量病变的患者（n=47）中，客观缓解率（ORR）为57.4% ，疾病控制率（DCR）高达83.0% ！ CT041治疗胰腺癌后，获得完全缓解的案例除了本次ASCO大会公布的惊艳数据外，CT041在治疗胰腺癌方面也展现出了不俗的成绩。全球著名期刊《血液学与肿瘤学杂志》，就曾报道过一个“ CT041治疗转移性胰腺癌后，获得完全缓解 ”的案例。本例幸运患者为一名75岁的女性，确诊为 pT2N0胰腺癌，既往虽接受了手术、化疗、放疗等传统治疗，但肿瘤依然进展，并出现肺部转移。由于该患者CLDN18.2 IHC 为3+，60%，符合CT041的入组标准，抱着最后一丝希望，她入组了CT041临床试验。入组后，先接受了淋巴细胞清除方案（环磷酰胺、氟达拉滨、白蛋白结合型紫杉醇）；之后接受 CT041回输治疗。结果显示，该患者在CT041输注后4周时，获得部分缓解（PR）；更令人惊叹的是，她肺转移的靶病灶随后消失，并达到完全缓解（CR）（详见下图）。而且直到2023年7月18日最后一次随访时，她的肿瘤仍得到良好控制。 ▼该例患者CT041治疗前后，影像学对比 ▲图源“Penn Medicine News”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除注：“红色箭头”表示：目标病变；“★”表示：原发病变。小编寄语 2024年度ASCO大会即将落下帷幕，除了上文提到的我国自研的多款CAR-T细胞疗法外，还有各国众多最新的抗癌研究进展相继公开，全球肿瘤医生网医学部后续也会及时为大家更新与会内容，敬请期待！癌症作为一种极其复杂且高度突变的复杂疾病，严重威胁患者的健康。随着医学技术的不断发展，如何让癌症患者活得更久、生存质量更高、复发的风险更低，逐渐成为当今各国科研人员的热门研究方向！值得欣慰的是，近年来，以过继性免疫细胞治疗（如CAR-T、TCR-T疗法）、癌症疫苗等为代表的肿瘤免疫疗法，逐渐成了继手术、化疗、放疗后的第四种肿瘤治疗方法。此外，更是涌现出了一批新型的抗癌手段：比如通过基因检测，选择特定的抗癌靶向药；及时存储TIL细胞，以预防肿瘤复发或作为晚期末线治疗手段；适当补充益生菌、调整肠道菌群，充分利用人体第二大免疫器官-肠道，来增加免疫治疗效果 …… 参考资料 [1]QI C,et al.Phase I study of GUCY2C CAR-T therapy IM96 in patients with metastatic colorectal cancer[J].2024. https://ascopubs-org.libproxy1.nus.edu.sg/doi/10.1200/JCO.2024.42.16_suppl.2518 [2]Aparicio C,et al.Cell therapy for colorectal cancer: the promise of chimeric antigen receptor (CAR)-T cells[J]. International journal of molecular sciences, 2021, 22(21): 11781. https://www.mdpi.com/1422-0067/22/21/11781 [3]QI C,et al.Claudin18. 2-targeted chimeric antigen receptor T cell-therapy for patients with gastrointestinal cancers: Final results of CT041-CG4006 phase 1 trial[J]. 2024. https://ascopubs-org.libproxy1.nus.edu.sg/doi/10.1200/JCO.2024.42.16_suppl.2501 [4]Huang H,et al.OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS)[J]. 2024. https://meetings.asco.org/abstracts-presentations/239043 [5]Hu Y,et al.Sequential CD7 CAR T-cell therapy and allogeneic HSCT without GVHD prophylaxis[J]. New England Journal of Medicine, 2024, 390(16): 1467-1480. https://www-nejm-org.libproxy1.nus.edu.sg/doi/full/10.1056/NEJMoa2313812 [6]Qi C,et al.CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer. J Hematol Oncol.2023 Sep 9;16(1):102. https://jhoonline-biomedcentral-com.libproxy1.nus.edu.sg/articles/10.1186/s13045-023-01491-9

ASCO会议细胞疗法免疫疗法临床结果临床1期

2024-06-05

·PRNewswire

Oricell Presented Long-term Follow-up Data of OriCAR-017 in RRMM at 2024 ASCO Annual Meeting, Highlighting the Sustained Efficacy of GPRC5D CAR-T Therapy

SHANGHAI and ROSELAND, N.J., June 5, 2024 /PRNewswire/ -- Oricell Therapeutics, a pioneering clinical-stage biopharmaceutical company, has presented the two-year long-term follow-up results of OriCAR-017, an open-label Phase I study evaluating GPRC5D-targeted CAR-T therapy in patients with relapsed/refractory multiple myeloma (RRMM), in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Efficacy & Durability of OriCAR-017 in RRMM Patients The updated data demonstrates that OriCAR-017 elicits deep and durable responses in RRMM patients as well as a favorable safety profile, including those refractory to anti-CD38 therapies, PIs, IMIDs, and those who have failed BCMA targeting CAR-T treatment. The long-term efficacy and safety follow-up results support OriCAR-017 as a promising therapeutic approach for RRMM. Currently, Oricell is smoothly advancing the clinical development of OriCAR-017 in both China (NCT06182696) and the United States (NCT06271252). As of January 16, 2024, all ten patients responded well to OriCAR-017, with the last patient having completed a 24-month follow-up. The overall response rate (ORR) was 100.0%, with a stringent complete response rate (sCR) of 80.0% and a very good partial response rate (VGPR) of 20.0%. All patients achieved 100% minimal residual disease negativity (MRD) at day 28, which was further confirmed as 100% negative at the 3-months follow-up. The median duration of response (mDoR) was 10.43 months (95% CI, 5.00-17.00), the median progression-free survival (mPFS) was 11.37 months (95% CI, 5.93-18.00), and the median overall survival (mOS) had not yet been reached (7 patients were still under survival follow-up, 1 patient died due to disease progression, and 2 patients died from COVID-19). In the high-dose group, where 67% of patients were previously treated with BCMA CAR-T, the mDoR was 17.23 months (95% CI, 7.33-NR), and the mPFS was 19.10 months (95% CI, 8.30-NR). Currently, a BCMA CAR-T-treated patient is still in remission (>24 months). Safety Profile of OriCAR-017 in the Treatment of RRMM The therapy was well-tolerated, with 9 out of 10 patients (90%) experiencing Grade 1 cytokine release syndrome (CRS) and only 1 patient (10%) experiencing Grade 2 CRS. No Grade 3 or higher CRS was observed. The median time to CRS onset was 2 days (range 1-9 days), with a median duration of 6 days (range 3-9 days). No immune effector cell-associated neurotoxicity syndrome (ICANS) or dose-limiting toxicities (DLTs) were observed. There were no serious adverse events (SAEs) or treatment-related deaths, cerebellar disorders, or delayed infections reported. Pharmacokinetics (PK) of OriCAR-017 in RRMM Patients There were no pharmacokinetic differences between dose levels, with a Cmax of 7354.7 copies/μL and an AUC0-28 of 68587 copies•day/μg. At high doses, CAR-T cells were still detectable at 9 months, and after 21 months of follow-up, one patient had CAR-T cell expansion above the lower limit of quantitation (LLOQ). Patients with Tlast ≥ 9 months had a longer PFS compared to those with Tlast < 9 months. G5 Expression in Response to OriCAR-017 Treatment in RRMM No correlation was observed between antigen expression and therapeutic efficacy. Baseline data from all patients showed positive GPRC5D expression in bone marrow CD138+ plasma cells (MMPC), while 50% of relapsed patients showed downregulated expression detected by flow cytometry. OriCAR-017 Demonstrates Significant Potential in Severely Progressed RRMM Patients It's worth noting that the study included patients with complex and advanced disease characteristics. Among the ten R/R MM patients, 40% had extramedullary disease (EMD), 50% had undergone one or more BCMA-directed CAR-T treatments, 70% had high-risk cytogenetics, 70% were classified as ECOG 2 score status, and 80% were at International Staging System (ISS) stages II & III. OriCAR-017 demonstrates its potential as a safe and efficacious treatment option for RRMM patients, marking a substantial progress in the fight against multiple myeloma and offering hope to those facing demanding health conditions. Details for the presentation as below: Oral Presentation #7511 Title: OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS). Session Type:Rapid Oral Abstract Session Session Title: Hematologic Malignancies—Plasma Cell Dyscrasia Link: About OriCAR-017 OriCAR-017, a chimeric antigen receptor (CAR) T cell therapy targeting GPRC5D, is a groundbreaking innovation in the treatment of relapsed/refractory multiple myeloma (RRMM). Leveraging Oricell Therapeutics' cutting-edge proprietary technology platforms, OriCAR-017 exhibits clearly differentiated binding avidity, persistence, anti-tumor efficacy and safety profile. OriCAR-017 received IND approval from FDA in Jan 2024 after its approval by NMPA in 2023. Impressive clinical results from the POLARIS study continue to be released. Currently, Oricell has assembled a skilled team to operate in both the U.S. and China, collaboratively accelerating pipeline development globally. SOURCE OriCell Therapeutics Co., Ltd.

临床结果细胞疗法临床1期ASCO会议免疫疗法

2024-06-01

·药明康德

总缓解率100%的CAR-T疗法；使近70%患者癌细胞完全消失的细胞疗法再获FDA加速批准…… | CGT周报

▎药明康德内容团队编辑近期，全球细胞和基因疗法（CGT）领域迎来系列进展。百时美施贵宝（Bristol Myers Squibb）嵌合抗原受体（CAR）T细胞疗法Breyanzi再获FDA加速批准，用于治疗套细胞淋巴瘤（MCL）。原启生物（Oricell Therapeutics）的CAR-T药物OriCAR-017在治疗复发/难治性多发性骨髓瘤的1期临床试验中表现亮眼，患者的总缓解率达100%。全球首款肿瘤浸润淋巴细胞（TIL）疗法再传捷报，与PD-1抑制剂联用一线治疗晚期黑色素瘤的完全缓解率（CR）达30%。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。图片来源：123RF———✦研发进展✦———◇ 百时美施贵宝宣布，美国FDA已批准其CAR-T细胞疗法Breyanzi（lisocabtagene maraleucel；liso-cel）的扩展适应症，用于既往接受过至少2线系统性疗法的复发性或难治性套细胞淋巴瘤成人患者，包括曾接受过布鲁顿酪氨酸激酶（BTK）抑制剂治疗的患者。根据新闻稿，Breyanzi是首个获美国FDA批准用于治疗四种不同亚型非霍奇金淋巴瘤的CAR-T疗法，使之能够治疗广泛的B细胞恶性肿瘤患者群体。在支持Breyanzi此次获批的临床试验中，根据2014 Lugano分类标准以及骨髓活检确认，85.3%（58/68）的患者有缓解，67.6%（46/68）的患者达到CR。51.4%的缓解者在12个月时仍保持缓解，38.8%的缓解者在18个月时仍保持缓解。Breyanzi是一种靶向CD19抗原的自体CAR-T细胞疗法，具有明确的组成和4-1BB共刺激域。它于2021年2月获FDA批准，用于治疗接受过两种或以上系统治疗的复发/难治性大B细胞淋巴瘤（LBCL）成人患者。Breyanzi在今年获加速批准用以治疗复发/难治性慢性淋巴细胞白血病（CLL）或小淋巴细胞淋巴瘤（SLL）、复发/难治性滤泡性淋巴瘤（FL）成人患者。◇ Iovance Biotherapeutics公司公布了其TIL疗法Amtagvi（lifileucel）与PD-1抑制剂Keytruda（pembrolizumab）联合用于一线治疗晚期黑色素瘤的最新临床数据。分析显示，接受治疗的晚期黑色素瘤患者获得深度、持久的应答，患者的客观缓解率达65%，CR率达30%。Iovance已经启动3期临床试验TILVANCE-301，评估这一组合疗法一线治疗晚期黑色素瘤的效果。Lifileucel是基于患者自身的肿瘤浸润淋巴细胞构建的细胞疗法，其可识别并靶向多种患者特异性新抗原，以介导肿瘤细胞死亡。Lifileucel在今年2月获FDA加速批准用于治疗晚期黑色素瘤。该疗法是全球首款获批的TIL疗法，也是首款获批治疗实体瘤的T细胞疗法，是细胞疗法的又一里程碑。◇ Kiromic BioPharma公司公布了其在研γ-δ T细胞（GDT）疗法Deltacel（KB-GDT-01）用于治疗IV期转移性非小细胞肺癌（NSCLC）患者的1期临床试验的积极早期疗效数据。该研究中，第二个队列首名患者接受治疗六周后的初步结果显示，Deltacel在控制肿瘤生长方面具有有效性，并显示出良好的安全性和耐受性。扫描显示患者的疾病稳定，未发现新的转移灶，肿瘤缩小了8.5%。此外，Deltacel治疗使患者无需使用处方止痛药，生活质量得到改善。Deltacel是一种同种异体细胞治疗产品，由未经修饰的供体来源GDT组成。Deltacel旨在利用GDT的天然效力靶向实体瘤，最初的临床开发重点是NSCLC（约占肺癌病例的80%至85%）。两项临床前研究的数据表明，Deltacel与低剂量放射治疗相结合具有良好的安全性和有效性。◇ Be Biopharma公司宣布美国FDA批准了其潜在“first-in-class”的自体B细胞疗法（BCM）BE-101的IND申请。BE-101旨在将人类FIX基因插入原代人类B细胞，从而表达可治疗血友病B的活性FIX。在临床前研究中，单次使用BE-101已被证明能够提供具活性和持续的FIX水平。数据证实了表达FIX的BCM能够在骨髓组织中按预期分布，并能在骨髓组织中长期稳定地定植。此外，BE-101的可重复给药性也得到了证实，血浆FIX水平如预期增加。该公司计划在2024年下半年启动一项1/2期临床试验，以评估BE-101在中重度至重度血友病B成年患者中的安全性和初步疗效。◇ 原启生物公布了其靶向GPRC5D的CAR-T药物OriCAR-017治疗复发/难治性多发性骨髓瘤的1期临床试验的2年长期随访结果。截至2024年1月16日的数据，所有（10名）患者对OriCAR-017治疗应答良好，总缓解率为100.0%，严格完全缓解（sCR）率为80.0%，非常好的部分缓解率（VGPR）为20.0%。所有患者在第28天都达到了100%微小残留病灶阴性率（MRD），且在第3个月得到进一步检测确认为100%阴性。中位缓解持续时间（mDoR）为10.43个月；中位无进展生存期（mPFS）为11.37个月；中位总生存期（mOS）尚未达到。在高剂量组中（67%为BCMA CAR-T经治患者），其mDoR为17.23个月，mPFS为19.10个月。此外，OriCAR-017显示良好的安全性和耐受性。◇ 锐正基因公布了其体内基因编辑药物ART001治疗转甲状腺素蛋白淀粉样变性（ATTR）患者的24周临床安全性和药效观察结果。研究结果显示，给药后4周，高剂量组受试者外周TTR蛋白较基线即可平均下降90%以上；给药24周后，高剂量组受试者ART001药效稳定在90%以上，并初步显示出一次性给药即可获得长期持续药效的潜力。在安全性方面，10例受试者未发生输注相关反应，未发生与药物相关的严重不良事件或严重不良反应，也未见肝毒性和免疫毒性。在脱靶编辑方面，ART001在人体细胞实验中，即使超过饱和剂量近80倍，都检测不到脱靶编辑。ART001注射液为锐正基因自主研发，以脂质纳米颗粒（LNP）作为递送载体，将靶向TTR基因的基因编辑组件递送至肝脏，安全特异地编辑TTR基因，阻断TTR蛋白的表达，从而避免产生淀粉样物质异常沉积。———✦融资、合作、M&A✦———图片来源：123RF◇ Anocca公司与Shinobi Therapeutics公司宣布建立战略合作伙伴关系，将Shinobi公司专有的免疫逃避iPS-T细胞平台结合由Anocca公司发现并验证的新型候选T细胞受体（TCR），开发一类用于治疗实体瘤的新型现货型同种异体TCR工程iPS-T细胞疗法（TCR-iPS-T）。Shinobi公司的“Katana”技术能以即插即用的方式将抗原靶向TCR和/或CAR构建体有效地导入其免疫逃避iPS-T细胞。Anocca开发了一种独特的发现平台，利用可编程的人体细胞能够重建和操纵T细胞免疫，并提供高度特异性、可临床应用的TCR候选库，用于治疗实体瘤。▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Be Biopharma Announces FDA Clearance of IND Application for BE-101 in Hemophilia B. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528592948/en[2] Kiromic BioPharma Reports Favorable Results at Six Weeks from Fourth Patient in Deltacel-01 Clinical Trial. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240529675813/en[3] U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi as a New CAR T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma. Retrieved May 30, 2024 from https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-as-a-New-CAR-T-Cell-Therapy-for-Relapsed-or-Refractory-Mantle-Cell-Lymphoma/default.aspx[4] Iovance Biotherapeutics Announces Clinical Data in Frontline Advanced Melanoma at ASCO 2024 Annual Meeting. Retrieved May 24, 2024 from https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-clinical-data-frontline[5] 2024 ASCO: 原启生物OriCAR-017 口头报告摘要公布. Retrieved May 24 , 2024, from https://mp.weixin.qq.com/s/P7tofaL9SRqyv3zCJJcv6Q[6] 中国首个进入IIT临床研究的体内基因编辑产品锐正基因ART001将发布最新24周临床研究数据. Retrieved May 27 , 2024, from https://mp.weixin.qq.com/s/sD4xW6CJ8vamEK88IfckTQ[7] Anocca AB and Shinobi Therapeutics Announce Strategic Partnership to Develop Allogeneic TCR-T Cell Therapies in Oncology. Retrieved May 31, 2024 from https://www.globenewswire.com/news-release/2024/05/30/2890550/0/en/Anocca-AB-and-Shinobi-Therapeutics-Announce-Strategic-Partnership-to-Develop-Allogeneic-TCR-T-Cell-Therapies-in-Oncology.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

细胞疗法免疫疗法临床结果加速审批临床3期

100 项与靶向GPRC5D嵌合抗原受体自体T细胞（原启生物）相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
多发性骨髓瘤	临床2期	中国	原启生物科技（上海）有限责任公司	2023-10-26

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05016778 (POLARIS, ASCO2024) 人工标引	临床1期	复发性多发性骨髓瘤 \| 多发性骨髓瘤	10	OriCAR-017	淵膚鏇鹹淵襯衊繭築齋(鏇蓋鹽襯範艱齋齋觸糧) = 積襯窪襯憲鹽鹹淵襯製膚範衊蓋膚獵齋簾製網 (遞醖餘繭獵積構鹹觸選 ) 更多	积极	2024-05-24
NCT05016778 (POLARIS, ASCO2024) 人工标引	临床1期	复发性多发性骨髓瘤 \| 多发性骨髓瘤	10	OriCAR-017	淵膚鏇鹹淵襯衊繭築齋(鏇蓋鹽襯範艱齋齋觸糧) = 顧艱遞艱壓廠遞鑰衊壓膚範衊蓋膚獵齋簾製網 (遞醖餘繭獵積構鹹觸選 ) 更多	积极	2024-05-24
NCT05016778 (POLARIS, Literature) 人工标引	临床1期	多发性骨髓瘤	13	OriCAR-017	襯襯觸夢鏇衊觸觸醖艱(獵膚憲鑰顧簾繭選範蓋) = not identified 選窪壓膚製願醖壓窪夢 (遞醖鬱網鏇構艱選鹹憲 ) 更多	积极	2024-02-01
NCT05016778 (POLARIS, PRNewswire) 人工标引	早期临床1期	复发性多发性骨髓瘤	10	OriCAR-017	繭窪選醖壓構範淵艱構(艱壓鬱餘築觸鹽鏇夢憲) = 壓積窪襯製鏇繭淵鏇製鏇鹹積衊糧鬱願鏇淵範 (醖鑰齋壓鹽壓夢餘蓋觸 ) 更多	积极	2023-01-30
NCT05016778 (POLARIS, PRNewswire) 人工标引	早期临床1期	复发性多发性骨髓瘤	10	OriCAR-017 (relapsed after BCMA CAR T-cell therapy)	膚製窪製鹽憲艱獵遞繭(網壓構構醖顧鏇繭憲範) = 鹽選積醖衊窪獵製範壓繭遞膚蓋艱壓廠衊蓋夢 (窪網艱艱淵築蓋襯廠夢 ) 更多	积极	2023-01-30
NCT05016778 (POLARIS, ASCO2022) 人工标引	临床1期	复发性多发性骨髓瘤 \| 浆细胞骨髓瘤难治	11	OriCAR-017+Chemotherapy	網繭選鑰憲簾網窪觸憲(鹹選夢廠憲衊壓鏇蓋簾) = The most common TEAEs were neutropenia (G3/4 100%), thrombocytopenia (G3/4 100%), leukopenia (G3/4 100%), lymphopenia (G3/4 100%) and anemia (G3/4 87.5%). 網鑰鹽鏇憲顧鑰網鑰觸 (製鹽壓鬱繭積願遞蓋糧 ) 更多	积极	2022-06-02