Gavocabtagene autoleucel (gavo-cel; TC-210) is a novel cell therapy that consists of autologous genetically engineered T cells expressing a single-domain antibody that recognizes human Mesothelin, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex.
This Phase 1/2 study aims to establish the recommended Phase 2 dose (RP2D) and subsequently evaluate the efficacy of gavo-cel, with and without immuno-oncology agents, in patients with advanced mesothelin-expressing cancers, with overall response rate and disease control rate as the primary Phase 2 endpoints.

开始日期2019-04-15

申办/合作机构

TCR² Therapeutics, Inc.

[+1]

100 项与 Gavocabtagene autoleucel 相关的临床结果

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100 项与 Gavocabtagene autoleucel 相关的转化医学

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100 项与 Gavocabtagene autoleucel 相关的专利（医药）

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项与 Gavocabtagene autoleucel 相关的文献（医药）

2023-12-01·Cancer immunology, immunotherapy : CII

Functional enhancement of mesothelin-targeted TRuC-T cells by a PD1-CD28 chimeric switch receptor

Article

作者: Tighe, Robert ; Lofgren, Michael ; Watt, Amy ; Gutierrez, Dario A ; Kieffer-Kwon, Philippe ; Baeuerle, Patrick A ; McCarthy, Derrick ; Ding, Jian ; Hofmeister, Robert ; Kobold, Sebastian ; Horton, Holly

Abstract:

T cells expressing a mesothelin (MSLN)-specific T cell receptor fusion construct (TRuC®), called TC-210, have demonstrated robust antitumor activity in preclinical models of mesothelioma, ovarian cancer, and lung cancer. However, they are susceptible to suppression by the programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) axis and lack intrinsic costimulatory signaling elements. To enhance the function of anti-MSLN TRuC-T cells, chimeric switch receptors (CSRs) have been designed to co-opt the immunosuppressive PD-1/PD-L1 axis and to deliver a CD28-mediated costimulatory signal. Here, we report that coexpression of the PD1-CD28 CSR in TRuC-T cells enhanced T cell receptor signaling, increased proinflammatory effector cytokines, decreased anti-inflammatory cytokines, and sustained effector function in the presence of PD-L1 when compared with TC-210. Anti-MSLN TRuC-T cells engineered to coexpress PD1-CD28 CSRs comprising the ectodomain of PD-1 and the intracellular domain of CD28 linked by the transmembrane domain of PD-1 were selected for integration into an anti-MSLN TRuC-T cell therapy product called TC-510. In vitro, TC-510 showed significant improvements in persistence and resistance to exhaustion upon chronic stimulation by tumor cells expressing MSLN and PD-L1 when compared with TC-210. In vivo, TC-510 showed a superior ability to provide durable protection following tumor rechallenge, versus TC-210. These data demonstrate that integration of a PD1-CD28 CSR into TRuC-T cells improves effector function, resistance to exhaustion, and prolongs persistence. Based on these findings, TC-510 is currently being evaluated in patients with MSLN-expressing solid tumors.

2023-08-01·Nature medicine1区 · 医学

Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results

1区 · 医学

Article

作者: Ghafoor, Azam ; Hassan, Raffit ; Quintás-Cardama, Alfonso ; Shah, Nirali N ; Cao, Liang ; Oh, David Y ; Butler, Marcus ; Johnson, Melissa ; Ross, Michael ; Smalley, Munisha ; Tanyi, Janos L ; O'Cearbhaill, Roisin E ; Saboury, Babak ; Zikaras, Kevin ; Hong, David

Abstract:

The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent (n = 3) or after lymphodepletion (LD,n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 108cells per m2after LD. Grade 3 or higher pneumonitis was seen in 16% of all patients and in none at the RP2D; grade 3 or higher cytokine release syndrome occurred in 25% of all patients and in 15% at the RP2D. In 30 evaluable patients, the overall response rate and disease control rate were 20% (13% confirmed) and 77%, respectively, and the 6-month overall survival rate was 70%. Gavo-cel warrants further study in patients with mesothelin-expressing cancers given its encouraging anti-tumor activity, but it may have a narrow therapeutic window. ClinicalTrials.gov identifier:NCT03907852.

2001-01-01·Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics

[Activity in ISO/TC210]

Article

作者: Iinuma, Takeshi

项与 Gavocabtagene autoleucel 相关的新闻（医药）

2025-07-09

·今日头条

25天全身多处肿瘤消失！TCR-T疗法多点爆破肺癌、卵巢癌、肉瘤等

近期，全球权威医学期刊《Nature Medicine》报道的一项研究在抗癌领域引发轰动：一位67岁的腹膜间皮瘤（MPM）患者在尝试所有常规治疗方案无效后，接受了新型TCR-T疗法仅25天，其体内肿瘤便显著缩小，随后几乎完全消退，实现了临床意义上的“重获新生”。值得关注的是，这类带来突破的TCR-T免疫疗法中，一款名为“Afami-cel”的产品已于2024年8月在美国获批上市，用于治疗成年患者的不可切除或转移性滑膜肉瘤。更令人振奋的是，这款备受国际关注的疗法目前已在我国针对多种癌种启动多项临床研究，有望为全球患者带来新的治疗希望！ ▲截图源自“Nature medicine” gavo-cel TCR-T精准锁杀间皮瘤、卵巢癌、胆管癌等，77%疾病受控，一例治疗25天全身多处肿瘤消退间皮素是一种细胞表面糖蛋白，正常情况下仅在胸膜、腹膜和心包的间皮细胞中表达；但在约30%的人类癌症中存在过表达，这使其成为靶向治疗（包括T细胞疗法）中极具吸引力的肿瘤抗原。gavocabtagene autoleucel（gavo-cel）正是由单结构域抗间皮素抗体组成的一种新型疗法，该抗体可整合到内源性T细胞受体（TCR）中，在与间皮素结合后能启动TCR的完整信号传导，从而精准靶向癌细胞。全球权威期刊《Nature Medicine》报道了gavo-cel治疗难治性间皮素表达实体瘤的1/2期试验（NCT03907852）第1阶段数据，结果令人振奋。该研究共入组32例中位年龄为63岁（范围：28-84岁）的患者，包括23例间皮瘤、8例卵巢癌、1例胆管癌患者；其中3例接受gavo-cel单药治疗，29例在淋巴细胞清除（LD）后接受治疗gavo-cel治疗。结果显示：在30例可评估患者中，总缓解率（ORR）为20% （其中确诊部分缓解率13%），疾病控制率（DCR）达77%，6个月总生存率为70% 。除2例外，其余患者的靶病灶直径总和均缩小，减小幅度4%-80% （详见下图）；尤其值得注意的是，淋巴细胞清除（LD）后接受治疗的患者肿瘤消退更显著， 8例（5例间皮瘤、2例卵巢癌、1例胆管癌）缩小超过30% ，且消退程度与输注前肿瘤负荷无关。另有 1例间皮瘤患者（患者3）出现逐渐缓解，虽3个月时靶病灶消退不足30%，但 6个月时消退超30% 。 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除此外，所有患者的的中位无进展生存期（PFS）为5.6个月（95％CI，3.1–5.8，详见下图a），中位总生存期（OS）为10.6个月（95％CI，6.6–15.6，详见下图b）。 6个月OS为70.2％。 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除值得一提的是，有三例患者的治疗过程，直观展现了gavo-cel的疗效。其中一位67岁女性转移性上皮样间皮瘤患者（患者15），在4种前期治疗失败后，入组接受淋巴细胞清除（LD）+gavo-cel治疗。结果显示：治疗第5天，血清乳酸脱氢酶（LDH）升高（提示肿瘤细胞被杀伤），第9天达峰后逐渐下降。第25天的CT扫描显示肿瘤显著缩小（大部分已变为液体）， ¹⁸F-氟脱氧葡萄糖（FDG）摄取大幅降低，随后几乎完全消退。这种缓解状态持续了12个月（详见下图a、b）。治疗第64天的胸壁肿块活检显示：肿瘤完全坏死，且无任何间皮素表达。 ▼该患者输注gavo-cel前、输注后约1个月、输注后8个月获得的18F-FDGPET最大强度投影正面图 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除另一例36岁上皮样恶性腹膜间皮瘤男性（患者4），在检查点抑制剂治疗失败后接受了gavo-cel治疗，肿瘤明显消退：基线MRI与治疗后6个月的CT扫描对比显示，毗邻左肾的病变（病变1）已完全消退，直肠腹膜反射处的病变（病变2）也显著缩小（详见下图）。 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除还有一例70岁铂类难治性高级别浆液性卵巢癌女性（患者5），接受gavo-cel治疗后同样出现肿瘤消退：代表性CT扫描显示，治疗后1个月和3个月时，纵隔淋巴结（病灶1）与腹部腔静脉后淋巴结（病灶2）的靶病灶均持续缩小，且这一效果维持至治疗后6个月（详见下图）。 ▲图源“Nature medicine”，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 Lete-cel疗法精准锁定NY-ESO-1靶点，让2类难治肉瘤迎转机，总缓解率达40% Lete-cel是一种自体工程化T细胞受体疗法，其靶点为NY-ESO-1睾丸癌抗原——该抗原在滑膜肉瘤（SyS）和粘液样/圆细胞脂肪肉瘤（MRCLS）中高表达。初步研究已显示，在NY-ESO-1阳性的SyS或MRCLS患者中，Lete-cel展现出良好疗效。 2024年美国临床肿瘤学会（ASCO）大会上，Lete-cel的2期临床试验（NCT03967223）公布了惊艳数据。该研究共纳入73例转移性或不可切除的滑膜肉瘤（SyS）或粘液样/圆细胞脂肪肉瘤（MRCLS）患者，中位年龄为46.0岁（范围：18-68岁），均接受Lete-cel治疗。结果显示：在45例可评估疗效的患者中，总缓解率（ORR）达40% （18/45，20.3%-62.3%），其中包括2例完全缓解（CR）、16例部分缓解（PR）。中位缓解持续时间为10.6个月（95%CI：3.3-未达到）。 ▲图源“ASCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除细分癌种来看，滑膜肉瘤（SyS）患者缓解率为39% （9例），粘液样/圆细胞脂肪肉瘤（MRCLS）患者为41% （9例）。 ▲图源“ASCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除综上，Lete-cel在IGNYTE-ESOSS2研究的初始分析达到主要终点，为作为晚期或转移性SyS、MRCLS患者的新型疗法奠定了坚实基础，凸显出广阔应用潜力。 ADP-A2M10 TCR-T疗法精准攻坚非小细胞肺癌：71.4%患者病情受控，中位生存期达132天《免疫肿瘤学杂志》报道了一项关于ADP-A2M10细胞治疗非小细胞肺癌的I期临床研究（ADP-0022-003，NCT02592577），为非小细胞肺癌患者带来了新的曙光！该研究共纳入11例HLA-A*02阳性的晚期（IIIB或IV期）非小细胞肺癌患者，包括8例腺癌、3例鳞状细胞癌。入组后，所有患者均接受淋巴细胞清除术联合ADP-A2M10治疗——这种经基因改造的自体T细胞可表达MAGE-A10特异性T细胞受体（TCR）。结果显示：在7例可评估疗效的患者中，71.4%（5例）达到病情稳定（SD），中位无进展生存期（PFS）为58天，中位总生存期（OS）更是长达132天。尤为值得关注的是其中1例患者（患者9）：首次TCR-T细胞回输后，肿瘤显著缩小25% （详见下图）；在第2次输注8周后，进一步达到部分缓解（PR）。 ▼患者9在治疗前、治疗第12周、治疗结束时的CT图像对比 ▲图源“BMJ”，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： ①红色箭头：代表右下叶（RLL）肺肿块； ②蓝色箭头：代表左上叶（LUL）肺肿块。小编寄语 TCR-T疗法创新性地开创了“抗癌+抗病毒”双效合一的治疗范式。近年来，科研团队正加速探索其在病毒相关性实体瘤领域的应用，尤其是乙肝病毒引发的肝细胞癌，以及人乳头瘤病毒（HPV）相关的宫颈癌等重点癌种。值得振奋的是，随着2024年首款TCR-T细胞治疗产品成功获批上市，标志着这一前沿技术正式迈入临床应用阶段！我们期待未来有更多突破性抗癌疗法获批，助力实体瘤患者实现长期带瘤生存的希望。参考资料 [1]Hassan R,et al.Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results[J]. Nature medicine, 2023, 29(8): 2099-2109. https://www.nature.com/articles/s41591-023-02452-y [2]D'Angelo S P,et al.Lete-cel in patients with synovial sarcoma or myxoid/round cell liposarcoma: Planned interim analysis of the pivotal IGNYTE-ESO trial[J]. 2024. https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2500 [3]Blumenschein GR,et al.Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer. J Immunother Cancer. 2022 Jan;10(1):e003581. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796260/ 本文为全球肿瘤医生网原创，未经授权严禁转载

细胞疗法临床结果免疫疗法

2024-04-12

·FierceBiotech

Genentech axes Adaptimmune cell therapy deal as it presses ahead with staff cuts

Genentech is severing ties with Adaptimmune, backing out of a 2021 deal the Roche company had paid $150 million cash for. In the same week that Genentech confirmed it's cutting 3% of its staff, the Roche subsidiary has terminated a cell therapy partnership with Adaptimmune Therapeutics worth up to $3 billion biobucks. The collaboration, inked in 2021, was a licensing deal focused on the development of two types of allogeneic T-cell therapies: off-the-shelf therapies directed to up to five targets and personalized therapies using αβ T-cell receptors isolated from a patient, with these therapies being administered to the same patient. At the time, Genentech paid out $150 million in cash. Since then, Adaptimmune has earned $35 million in milestone payments. The deal termination will set in 180 days after notice of the decision was received, meaning the terms of the pact are effective until then, according to Securities and Exchange Commission filings. Adaptimmune received word of the termination on Wednesday, according to the filing. The Adaptimmune news comes shortly after Genentech confirmed to Fierce Biotech that it would be trimming roughly 3% of its workforce across "several departments.” Earlier this year, the biotech's parent company Roche announced cuts to its product development team. “Note that this limited reduction will allow us to shift resources to the areas that we believe can provide the greatest impact for patients,” a Genentech spokesperson told Fierce Biotech in an emailed statement. “We are actively hiring in a number of areas to bring forward our most promising molecules and capabilities, and we project that the overall workforce across Roche will remain stable throughout 2024.” For Adaptimmune, the termination comes almost exactly one year after another pharma discontinued work with the biotech. In April 2023, GSK paid Adaptimmune $37.3 million to wipe its hands of two programs, one of which included lete-cel, an asset the company at one point touted as its leading cell therapy. Then, in November, Adaptimmune axed two programs dubbed Gavo-cel and TC-510. After a review of safety and efficacy data for both candidates, the U.K. company said it didn’t “see a path forward” for further development of either programs. Now, the company has zoomed in on launching afami-cel—which has snagged FDA priority review and is slated for an FDA decision by or on August 4 of this year—for patients with advanced synovial sarcoma. "We've had a very valuable collaboration with our partner Genentech, and we continue to believe in the long-term potential of our iPSC-based allogeneic platform,” Adaptimmune CEO Adrian Rawcliffe said in an April 12 release. “Over the past 12 months, we've been resolutely focused on our late-stage autologous pipeline—in particular, our sarcoma franchise. We have the resources to deliver afami-cel to market as planned, and I look forward to updating on progress at our investor day next week."

细胞疗法引进/卖出优先审批

2024-02-01

·PRNewswire

Myeloid Expands Leadership Team with Robert Hofmeister, Ph.D., as Chief Scientific Officer

CAMBRIDGE, Mass., Feb. 1, 2024 /PRNewswire/ -- Myeloid Therapeutics, Inc. ("Myeloid"), a clinical stage oncology company, has appointed Robert Hofmeister, Ph.D., as Chief Scientific Officer (CSO). An expert in immuno-oncology, gene and cell therapy, Dr. Hofmeister brings more than 25 years of scientific leadership experience and a track record of drug discovery and early development. "As Myeloid advances our novel pipeline of programs, I am thrilled to welcome Dr. Hofmeister as our new Chief Scientific Officer. His successful track record leading drug discovery teams, which contributed to the approval of two drugs by the FDA, will be instrumental in building upon our achievements and navigating the promising opportunities ahead," said Daniel Getts, Ph.D., Myeloid CEO. Dr. Hofmeister's appointment comes at a crucial time when Myeloid has achieved numerous milestones, including a Phase 1 clinical study with MT-302 for patients with TROP2-expressing tumors. Notably, this study investigates the first in vivo mRNA CAR candidate to ever be dosed in patients. In the year ahead, the company is on track to advance its second in vivo CAR program to the clinic targeting GPC3-positive liver cancers. In addition to being a key member of the executive management team, Dr. Hofmeister will lead the expansion of Myeloid's cutting-edge RNA focused research and development efforts, aimed at designing novel therapeutics that target, deliver, and program immune cells to combat cancer and other deadly diseases. "I'm thrilled to work with Myeloid's world class team and cutting-edge in vivo engineering platform to revolutionize the treatment of cancer and autoimmune diseases, and make a difference in the lives of patients," Robert Hofmeister, Ph.D. "Myeloid's in vivo mRNA programming platform is positioned to dramatically change the future of cancer immunotherapy and the treatment of other devastating diseases." Before joining Myeloid, Dr. Hofmeister was the CSO at Resonance Medicine where he drove the development of their discovery platform for therapeutic proteases. Previously, he served as CSO at TCR2 Therapeutics where he started as employee number one and was instrumental in building and leading the R&D function, driving the development of their proprietary TRuC®-T cell platform from concept to first cleared IND (TC-210 program) and successfully contributed to taking the company public as well as securing multi-million dollar rounds of fundraising. Dr. Hofmeister also held various roles at EMD Serono where he was involved in the development of now approved Bavencio (avelumab) and building the company's immuno-oncology platform. He started his biotech career at Micromet AG, now Amgen Research Munich, where he helped shape the development of Blincyto (blinatumomab), the first FDA-approved bispecific antibody for the treatment of refractory ALL. Dr. Hofmeister received his Ph.D. from the University of Regensburg in Germany, where he studied the signaling of the cytokine interleukin-1. He continued to work in the cytokine field as a postdoctoral fellow at the National Cancer Institute. About Myeloid Therapeutics Myeloid Therapeutics is a clinical stage oncology company developing novel therapies for cancer. Integrating the fields of mRNA-based therapeutics, immunology, and cancer biology, the Company's proprietary platform provides clinical solutions for patients with solid tumors. Myeloid is headquartered in Cambridge, MA. For more information visit: . Media Contact: Jennifer Hanley Ridge Hill Group [email protected] Investor Contact Amy Conrad Juniper Point [email protected] SOURCE Myeloid Therapeutics, Inc.

临床1期高管变更免疫疗法上市批准

100 项与 Gavocabtagene autoleucel 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
晚期癌症	临床2期	美国	Bristol Myers Squibb Co.	2019-04-15
晚期癌症	临床2期	美国	TCR² Therapeutics, Inc.	2019-04-15
晚期癌症	临床2期	加拿大	Bristol Myers Squibb Co.	2019-04-15
晚期癌症	临床2期	加拿大	TCR² Therapeutics, Inc.	2019-04-15
胆管癌	临床2期	美国	Bristol Myers Squibb Co.	2019-04-15
胆管癌	临床2期	美国	TCR² Therapeutics, Inc.	2019-04-15
胆管癌	临床2期	加拿大	TCR² Therapeutics, Inc.	2019-04-15
胆管癌	临床2期	加拿大	Bristol Myers Squibb Co.	2019-04-15
卵巢高级别浆液性腺癌	临床2期	美国	TCR² Therapeutics, Inc.	2019-04-15
卵巢高级别浆液性腺癌	临床2期	美国	Bristol Myers Squibb Co.	2019-04-15

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03907852 (ASCO 12023 \| ASCO 22023) 人工标引	临床1/2期	Mesothelin阳性实体瘤 \| 间皮瘤 MSLN Expression	32	gavo-cel	夢繭築繭襯衊簾獵艱窪(積夢遞鏇觸繭蓋醖獵鏇) = no lymphodepletio;1x108/m2 獵積夢艱淵齋願構願構 (醖構鹹積網願網艱鏇壓 ) 更多	积极	2023-05-31
NCT03907852 (ASCO 12023 \| ASCO 22023) 人工标引	临床1/2期	Mesothelin阳性实体瘤 \| 间皮瘤 MSLN Expression	32	gavo-cel (MPM)		积极	2023-05-31
NCT03907852 (AACR2023) 人工标引	临床1期	腹膜恶性间皮瘤 \| 卵巢癌 \| 胆管癌	32	Gavocabtagene autoleucel	簾築鏇壓淵醖鏇淵襯鹹(鏇艱艱構選築糧鑰衊齋) = 簾選鑰鹹獵繭繭構製壓憲襯鹽網願網鑰窪遞壓 (顧膚鬱鹽膚衊鹽築觸選 )	积极	2023-04-14
NCT03907852 (ESMO2021) 人工标引	临床1/2期	Mesothelin阳性实体瘤	17	Gavocabtagene autoleucel	鹹膚願鹹艱衊蓋構製餘(網衊艱艱鑰觸憲鹽蓋廠) = One DLT (gr3 pneumonitis at DL1) and 2 gr3 CRS events were reported, both resolving with tocilizumab/corticosteroids. 簾範鹽範繭膚網遞憲繭 (窪窪網選鬱夢簾網廠築 )	积极	2021-09-17
NCT03907852 (AACR2021)	临床1期	Mesothelin阳性实体瘤	7	gavo-cel (TC-210)	醖範繭齋顧顧積齋糧願(鑰糧獵膚齋襯繭衊衊範) = 鬱鹽廠夢構襯觸醖餘獵顧範鹹齋鏇鏇觸蓋鏇製 (選鏇糧夢襯齋鏇醖壓齋 ) 更多	-	2021-07-01