The goal of this clinical trial is to test MGC018 in patients with relapsed or refractory Extensive-Stage Small-Cell Lung Cancer (ES-SCLC). The main question it aims to answer is:
• Does the administration of MGC018 achieve a clinically meaningful response rate of 25% in patients with relapsed or refractory ES-SCLC?
Participants enrolled in the trial will receive MGC018 through an intravenous (IV) infusion, every 28 days until disease progression or unacceptable toxicity. Tumor assessment will be done every 2 cycles (28 day cycles). Blood samples will be taken for biomarker analysis before treatment, on cycle 3 day 1, and at progression. A pretreatment biopsies will be done.

开始日期2024-04-15

申办/合作机构

Georgetown University Hospital

[+1]

NCT05551117

/ Completed临床2期

A Phase 2, Open-label, Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

Study CP-MGC018-03 is an open-label, two-part, Phase 2 study. Part 1 of the study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT). ARAT includes abiraterone, enzalutamide, or apalutamide.
Participants may have received up to 1 prior docetaxel-containing regimen, but no other chemotherapy agents.
This part of the study will assess the efficacy and tolerability of vobramitamab duocarmazine (MGC018) in two experimental arms (2.0 mg/kg every 4 weeks [Q4W] and 2.7 mg/kg Q4W) . Approximately 100 participants will be randomized 1:1.
Part 2 of the study will enroll participants with locally advanced or metastatic solid tumors. Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab duocarmazine at a dose of 2.7 mg/kg every 4 weeks. Up to 200 participants may be enrolled in Part 2.
In both parts, vobramitamab duocarmazine will be administered intravenously (IV) in clinic on Day 1 of each 4-week cycle. Vobramitamab duocarmazine will be administered until criteria for treatment discontinuation are met. Participants will undergo regular testing for signs of disease progression using computed tomography (CT) scans, magnetic resonance imaging (MRI), bone scans, and prostate-specific antigen (PSA) blood tests. Routine examinations and blood tests will be performed and evaluated by the study doctor.

开始日期2023-06-13

申办/合作机构

MacroGenics, Inc.

NCT05293496

/ Active, not recruiting临床1期

A Phase 1/1b Dose Escalation and Cohort Expansion Study of MGC018 in Combination With Checkpoint Inhibitor in Participants With Advanced Solid Tumors

Study CP-MGC018-02 is a study of vobramitamab duocarmazine (MGC018) in combination with lorigerlimab (MGD019). The study is designed to characterize safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and preliminary antitumor activity. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors including, but not limited to, metastatic castration-resistant prostate cancer (mCRPC), melanoma, pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, and renal cell carcinoma (RCC) will be enrolled.
Vobramitamab duocarmazine and lorigerlimab are administered separately on Day 1 of every 4-week (28-day) cycle at the assigned dose for each cohort. Participants who do not meet criteria for study drug discontinuation may receive study drugs for up to 2 years.
Tumor assessments are performed every 8 weeks (± 7 days) for the initial 6 months on study drugs, then every 12 weeks (± 21 days) until progressive disease (PD).
Participants will be followed for safety throughout the study. .

开始日期2022-04-19

申办/合作机构

MacroGenics, Inc.

100 项与 vobramitamab duocarmazine 相关的临床结果

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100 项与 vobramitamab duocarmazine 相关的转化医学

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100 项与 vobramitamab duocarmazine 相关的专利（医药）

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项与 vobramitamab duocarmazine 相关的文献（医药）

2023-09-01·Journal for immunotherapy of cancer

Antitumor activity of the investigational B7-H3 antibody-drug conjugate, vobramitamab duocarmazine, in preclinical models of neuroblastoma

Article

作者: Bonvini, Ezio ; Bensa, Veronica ; Giusto, Elena ; Cilli, Michele ; Corrias, Maria Valeria ; Ciampi, Eleonora ; Calarco, Enzo ; Loo, Derik ; Brignole, Chiara ; Perri, Patrizia ; Pastorino, Fabio ; Ponzoni, Mirco ; Astigiano, Simonetta

Introduction:

B7-H3 is a potential target for pediatric cancers, including neuroblastoma (NB). Vobramitamab duocarmazine (also referred to as MGC018 and herein referred to as vobra duo) is an investigational duocarmycin-based antibody-drug conjugate (ADC) directed against the B7-H3 antigen. It is composed of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody chemically conjugated through a cleavable valine-citrulline linker to aduocarmycin-hydroxybenzamideazaindole (vc-seco-DUBA). Vobra duo has shown preliminary clinical activity in B7-H3-expressing tumors.

Methods:

B7-H3 expression was evaluated by flow-cytometry in a panel of human NB cell lines. Cytotoxicity was evaluated in monolayer and in multicellular tumor spheroid (MCTS) models by the water-soluble tetrazolium salt,MTS, proliferation assay and Cell Titer Glo 3D cell viability assay, respectively. Apoptotic cell death was investigated by annexin V staining. Orthotopic, pseudometastatic, and resected mouse NB models were developed to mimic disease conditions related to primary tumor growth, metastases, and circulating tumor cells with minimal residual disease, respectively.

Results:

All human NB cell lines expressed cell surface B7-H3 in a unimodal fashion. Vobra duo was cytotoxic in a dose-dependent and time-dependent manner against all cell lines (IC50 range 5.1–53.9 ng/mL) and NB MCTS (IC50 range 17.8–364 ng/mL). Vobra duo was inactive against a murine NB cell line (NX-S2) that did not express human B7-H3; however, NX-S2 cells were killed in the presence of vobra duo when co-cultured with human B7-H3-expressing cells, demonstrating bystander activity. In orthotopic and pseudometastatic mouse models, weekly intravenous treatments with 1 mg/kg vobra duo for 3 weeks delayed tumor growth compared with animals treated with an irrelevant (anti-CD20) duocarmycin-ADC. Vobra duo treatment for 4 weeks further increased survival in both orthotopic and resected NB models. Vobra duo compared favorably to TOpotecan-TEMozolomide (TOTEM), the standard-of-care therapy for NB relapsed disease, with tumor relapse delayed or arrested by two or three repeated 4-week vobra duo treatments, respectively. Further increased survival was observed in mice treated with vobra duo in combination with TOTEM. Vobra duo treatment was not associated with body weight loss, hematological toxicity, or clinical chemistry abnormalities.

Conclusion:

Vobra duo exerts relevant antitumor activity in preclinical B7-H3-expressing NB models and represents a potential candidate for clinical translation.

2020-11-01·Molecular cancer therapeutics2区 · 医学

Preclinical Development of MGC018, a Duocarmycin-based Antibody–drug Conjugate Targeting B7-H3 for Solid Cancer

2区 · 医学

Article

作者: Moore, Paul A. ; Loo, Deryk ; Koenig, Scott ; Huang, Ling ; Li, Ying ; Li, Pam ; Ciccarone, Valentina ; Tamura, James ; Chen, Francine Z. ; Gaynutdinov, Timur ; Sharma, Sharad ; Yee-Toy, Nicholas C. ; Chiechi, Michael ; De Costa, Anushka ; Hotaling, Tim E. ; Son, Thomas ; Hooley, Jeff ; Brown, Jennifer G. ; Gorlatov, Sergey ; Barat, Bhaswati ; Chen, Yan ; Li, Hua ; Wolff, Christina R. ; Easton, Ann ; Scribner, Juniper A. ; Bonvini, Ezio

Abstract:

B7-H3, also referred to as CD276, is a member of the B7 family of immune regulatory proteins. B7-H3 is overexpressed on many solid cancers, including prostate cancer, renal cell carcinoma, melanoma, squamous cell carcinoma of the head and neck, non–small cell lung cancer, and breast cancer. Overexpression of B7-H3 is associated with disease severity, risk of recurrence and reduced survival. In this article, we report the preclinical development of MGC018, an antibody–drug conjugate targeted against B7-H3. MGC018 is comprised of the cleavable linker-duocarmycin payload, valine-citrulline-seco duocarmycin hydroxybenzamide azaindole (vc-seco-DUBA), conjugated to an anti-B7-H3 humanized IgG1/kappa mAb through reduced interchain disulfides, with an average drug-to-antibody ratio of approximately 2.7. MGC018 exhibited cytotoxicity toward B7-H3–positive human tumor cell lines, and exhibited bystander killing of target-negative tumor cells when cocultured with B7-H3–positive tumor cells. MGC018 displayed potent antitumor activity in preclinical tumor models of breast, ovarian, and lung cancer, as well as melanoma. In addition, antitumor activity was observed toward patient-derived xenograft models of breast, prostate, and head and neck cancer displaying heterogeneous expression of B7-H3. Importantly, MGC018 exhibited a favorable pharmacokinetic and safety profile in cynomolgus monkeys following repeat-dose administration. The antitumor activity observed preclinically with MGC018, together with the positive safety profile, provides evidence of a potentially favorable therapeutic index and supports the continued development of MGC018 for the treatment of solid cancers.

项与 vobramitamab duocarmazine 相关的新闻（医药）

2025-03-24

·抗体圈

研发决策风云：放弃一款，力推多款

MacroGenics 在仔细瞅了瞅最近两期的数据后，一咬牙，决定挥泪告别对自家一款超厉害的抗体 - 药物偶联物的研究啦。这可真是研发路上的一个大转折哟！暂停到放弃，vobra duo 的坎坷路早在 2023 年 11 月，这家生物技术公司就给 vobramitamab duocarmazine（vobra duo）的研究踩了刹车。当时他们还解释说，正眼巴巴地盼着 2 期单药前列腺癌试验的无进展生存期（PFS）数据呢。你瞧，vobra duo 这设计可牛了，弄了个能切割的肽连接子，就想着把 DNA - 烷基化 duocarmycin 药物 “小包裹” 精准地送到表达 B7 - H3 的实体瘤那儿。公司首席执行官斯科特・科尼格医学博士、哲学博士，当时跟投资者解释得那叫一个详细，说公司得综合看看最终的 PFS 数据、这疗法安不安全，再瞅瞅在其他研发项目的大背景下竞争情况咋样，才能决定要不要再给 vobra duo 投钱。尽管 MacroGenics 放弃了 vobramitamab duocarmazine（vobra duo），但公司首席执行官斯科特·科尼格医学博士、哲学博士表示，公司仍然认为 B7 - H3 作为靶点具有“潜力”。结果呢，如今数据出来咯，2mg/kg 和 2.7mg/kg 剂量组的中位放射学无进展生存期，一个是 9.5 个月，另一个是 10 个月。3 月 20 日，MacroGenics 在全年财报里还说，安全性数据 “跟之前透露的没啥两样”。然后，公司大手一挥，在声明里表示：“综合评估 vobra duo 的安全性和有效性，再看看内部资源和研发管线，我们决定不自己继续开发 vobra duo 啦，不过呢，打算找找把这个项目合作出去的机会。” 放弃一款，还有多款 “潜力股” 虽说 vobra duo 被放弃了，可科尼格还是很坚定地说，公司依旧觉得 B7 - H3这个靶点 “潜力无限” 呢。他还透露，公司对另一种抗 B7 - H3 抗体 - 药物偶联物 MGC026 的进展那是相当 “满意”。这 MGC026 可是基于 topoisomerase I inhibitor（拓扑异构酶 I 抑制剂）的抗体 - 药物偶联物，眼下正在对晚期实体瘤患者进行 1 期剂量递增研究呢。另外，公司还有个叫 MGC028 的抗体 - 药物偶联物也处在临床阶段，它也是基于 topoisomerase Iinhibitor，专门靶向 ADAM9，最近才刚开始在实体瘤里进行 1 期研究。期待新数据，研发不停步 MacroGenics 现在满心期待着今年晚些时候 lorigerlimab 的数据。这 lorigerlimab 可是个 PD - 1xCTLA - 4 双特异性抗体，公司正把它和多西他赛联合起来，用在 2 期前列腺癌试验里呢。科尼格在昨天盘后发布的声明里兴奋地说：“2024 年我们完成了好多临床开发的大目标，像 LORIKEET 2 期研究的入组工作都完成啦，这研究可是评估 lorigerlimab 和多西他赛联合用在 mCRPC 患者身上效果的哟。” 他还补充道：“2025 年，我们可得接着这股劲儿，努力推进我们那些创新的临床候选产品管线，像 lorigerlimab、MGC026 和 MGC028，都得加把劲啦！” 值得一提的是，2025 年初，MacroGenics 兜里还有 2.017 亿美元的现金储备呢，公司估计这些钱能撑到 2026 年下半年，看来研发资金暂时有着落咯，就看这些研发项目能不能一路 “开挂” 啦！参考资料： https://www.fiercebiotech.com/biotech/macrogenics-pulls-plug-vobra-duo-adc-after-seeing-phase-2-prostate-cancer-data 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

临床2期财报临床终止临床1期

2025-03-21

·FierceBiotech

MacroGenics pulls plug on vobra duo ADC after seeing phase 2 prostate cancer data

Despite giving up on vobra duo, MacroGenics CEO Scott Koenig, M.D., Ph.D., said that the company still believes B7-H3 has “potential” as a target.\n MacroGenics has made the final decision to abandon work on one of its more advanced antibody-drug conjugates after taking a look at the latest phase 2 data.The biotech had already paused work on vobramitamab duocarmazine (vobra duo) back in November, explaining that it was awaiting progression-free survival (PFS) data from a phase 2 monotherapy prostate cancer trial. Vobra duo has a cleavable peptide linker designed to deliver a DNA-alkylating duocarmycin payload to solid tumors that express B7-H3.CEO Scott Koenig, M.D., Ph.D., explained to investors at the time that the company would make a call on whether to invest further in vobra duo after considering the final PFS data, the therapy’s safety profile and the competitive landscape in the context of the rest of its pipeline.The results are now in, and they show a median radiographic PFS of 9.5 months and 10 months for the 2-mg/kg and 2.7-mg/kg doses, respectively. Safety data “remained consistent with prior data disclosures,” MacroGenics said in its full-year earnings results March 20.“Based on its assessment of the vobra duo safety and efficacy profile and an internal resource and portfolio review, MacroGenics has decided not to pursue further internal development of vobra duo and will instead explore potential alternatives for partnering this program,” the company said in the release.Despite giving up on vobra duo, Koenig said the company still believes B7-H3 has “potential” as a target, adding that the biotech is “pleased with the progress being made with our alternate anti-B7-H3 ADC, MGC026.” MGC026, which is a TOP1i-based ADC, is undergoing a phase 1 dose-escalation study in patients with advanced solid tumors. The biotech also has another ADC in the clinic in the form of MGC028, a TOP1i-based ADC that targets ADAM9 and recently started a phase 1 study in solid tumors.MacroGenics is awaiting a readout later this year for lorigerlimab, a PD-1xCTLA-4 bispecific that the company is testing in a phase 2 prostate cancer trial in combination with docetaxel.“We concluded 2024 with the achievement of multiple clinical development milestones, including the completion of enrollment in the LORIKEET phase 2 study evaluating lorigerlimab in combination with docetaxel in patients with mCRPC,” Koenig said in yesterday\'s postmarket release.“We look forward to building upon this momentum in 2025 as we work to advance our novel pipeline of clinical product candidates, including lorigerlimab, MGC026 and MGC028,” the CEO added.MacroGenics entered the year with $201.7 million in the bank, which the company expects to last into the second half of 2026.

临床1期抗体药物偶联物临床2期

2024-11-06

·Firstwordpharma

MacroGenics' ADC moves one step closer to the drug development graveyard

MacroGenics is pulling back even further on the reins of lead antibody-drug conjugate (ADC) vobramitamab duocarmazine (vobra duo). The biotech said in its quarterly earnings report Tuesday that development of the B7-H3-targeting ADC is officially paused until it has complete safety and efficacy data from the Phase II TAMARACK study in-hand.Whether those results will support continued work on vobra duo, formerly MGC018, remains to be seen. Patient dosing in TAMARACK, which had been enrolling individuals with metastatic castration-resistant prostate cancer (mCRPC), was paused in July shortly after the company reported five patient deaths in the trial. MacroGenics expects to have mature median progression-free survival data from TAMARACK in early 2025.Stopped studiesThe development pause affects a Phase I/II trial of the ADC in solid tumours other than mCRPC, including non–small-cell lung cancer, triple-negative breast cancer, squamous cell carcinoma of the head and neck, and melanoma.A Phase I combination study of vobra duo plus MacroGenics' experimental PD-1/CTLA-4 bispecific lorigerlimab will also remain on hold. That trial was enrolling patients with relapsed or refractory, unresectable, locally advanced or metastatic solid tumours.MacroGenics said that, in addition to the TAMARACK safety and efficacy data, its development decision on vobra duo will be based on the competitive landscape for mCRPC, clinical resource availability, and potential partnering opportunities for the ADC.

抗体药物偶联物临床1期临床2期临床终止

100 项与 vobramitamab duocarmazine 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
去势抵抗性前列腺癌	临床3期	美国	MacroGenics, Inc.	2022-07-11
黑色素瘤	临床3期	美国	MacroGenics, Inc.	2022-07-11
非小细胞肺癌	临床3期	美国	MacroGenics, Inc.	2022-07-11
广泛期小细胞肺癌	临床2期	美国	MacroGenics, Inc.	2024-04-15
肛门肿瘤	临床2期	美国	MacroGenics, Inc.	2023-06-13
肛门肿瘤	临床2期	澳大利亚	MacroGenics, Inc.	2023-06-13
肛门肿瘤	临床2期	比利时	MacroGenics, Inc.	2023-06-13
肛门肿瘤	临床2期	法国	MacroGenics, Inc.	2023-06-13
肛门肿瘤	临床2期	意大利	MacroGenics, Inc.	2023-06-13
肛门肿瘤	临床2期	波兰	MacroGenics, Inc.	2023-06-13

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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


NCT05551117 (TAMARACK, ESMO2024) 人工标引	临床2期	转移性去势抵抗性前列腺癌	176	Vobra duo 2.0 mg/kg	顧繭範網艱憲觸醖衊構(鏇壓網窪憲衊選鹽築鬱) = 積淵襯遞獵獵鹽築簾鬱觸襯鹹選鑰製壓膚願淵 (鏇齋齋夢範鬱膚構襯鹹, 57 ~ 79) 更多	积极	2024-09-15
				Vobra duo 2.7 mg/kg	顧繭範網艱憲觸醖衊構(鏇壓網窪憲衊選鹽築鬱) = 壓憲觸壓糧壓膚糧蓋餘觸襯鹹選鑰製壓膚願淵 (鏇齋齋夢範鬱膚構襯鹹, 58 ~ 79) 更多
NCT05551117 (Tamarack, GlobeNewswire) 人工标引	临床2期	转移性去势抵抗性前列腺癌	176	Vobramitamab duocarmazine (vobra duo) 2.0 mg/kg q4W	鏇觸淵選憲鹹膚夢顧壓(繭鑰餘鑰鬱選醖蓋願膚) = 鹹餘遞廠選憲願鹹衊簾襯願蓋憲積壓憲襯壓鹽 (憲鑰衊鑰憲艱觸鹹顧襯 ) 更多	积极	2024-05-09
				Vobramitamab duocarmazine (vobra duo) 2.7 mg/kg q4W	鏇觸淵選憲鹹膚夢顧壓(繭鑰餘鑰鬱選醖蓋願膚) = 鹹醖簾糧艱齋艱鑰齋製襯願蓋憲積壓憲襯壓鹽 (憲鑰衊鑰憲艱觸鹹顧襯 ) 更多
NCT05551117 (TAMARACK, Corporate Publications) 人工标引	临床2期	转移性去势抵抗性前列腺癌	177	Vobra duo 2.0 mg/kg	窪鹽獵築構構鹽廠夢製(窪觸觸獵衊獵鏇齋蓋築) = 鹽鬱蓋選糧網夢壓遞鹽齋齋製憲觸廠構壓壓遞 (顧觸餘繭願衊範積築餘 ) 更多	积极	2024-04-03
				Vobra duo 2.7 mg/kg	窪鹽獵築構構鹽廠夢製(窪觸觸獵衊獵鏇齋蓋築) = 簾醖鏇觸衊簾獵餘獵齋齋齋製憲觸廠構壓壓遞 (顧觸餘繭願衊範積築餘 ) 更多
NCT03729596 (MGC018, ESMO2021)	临床1期	HR阳性/HER2低表达实体瘤	49	MGC018 3 mg/kg IV	糧壓願鬱繭製遞製繭夢(顧餘遞製遞願遞壓餘構) = 獵蓋簾築蓋壓選鏇鬱窪鏇積顧獵壓觸廠淵膚鑰 (廠製憲襯觸膚餘顧蓋壓 )	-	2021-09-16
NCT03729596 (ASCO 12021 \| ASCO 22021) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	29	MGC018	願網獵獵壓繭網網鬱鹽(範蓋積鑰衊齋鹹蓋壓獵) = 淵鹹餘淵繭構壓憲願廠蓋顧簾蓋糧憲窪積憲襯 (簾壓窪廠鹽構鹽窪齋廠 ) 更多	积极	2021-05-28