A Phase Ib Study of OBT076 or OBT076 Followed by Balstilimab in Patients With Recurrent or Metastatic (R/M) Adenoid Cystic Carcinoma (AdCC) of the Head and Neck (H&N)

Adenoid cystic carcinoma (AdCC) is a rare salivary gland malignant tumor that accounts for approximately 1-3% of all head and neck cancers. AdCC is often charaterised by a long natural history with a propensity for indolent but relentless growth and dissemination. Local recurrences and late distant metastases are common findings in about 35% of the patients and associated with a poor prognosis1. AdCC is among the most lethal salivary gland tumors2 with no proven therapy for metastatic disease. Little is known about endogenous immune response directed against AdCC. However, in a relatively large series of 28 AdCC tumor, the immune profiling has shown in most tumors high and frequent programmed death ligand 2 (PD-L2) expression and PD-L1 was generally not expressed on tumor and infiltrating cells3.
The Antibody Drug Conjugates (ADCs) are emerging as a novel therapeutic option in cancer treatment that looks promising for solid tumors. An experimental CD205/Ly75-directed ADC, OBT076 induce potent cytotoxic and antitumor activity. Recently, the combination of immunohistochemistry (IHC) and tissue micro array (TMA) was performed in a series of 46 AdCC, showing a unique profile with both frequent and high expression of CD205/Ly75, much higher than for other solid tumors. In a phase I study, OBT076 demonstrated promising results for 3 patients with 2 partial responses and 1 complete response for a gastric cancer4. In this last patient, analysis showed an increase in PD1+, CD4+ and CD8+ cells suggesting that OBT076 activates the patient's immune response against the tumor, especially PD-1 targeted therapies4.
Based on this rational and on the high level of expression of CD205/Ly75 in AdCC, the hypothesis tested in this study is that OBT076 could be a potential effective treatment for R/M AdCC, which is an orphan lethal disease. The efficacy of OBT076 will be tested either alone or followed by an anti PD-1 inhibitor (Balstilimab) with the hypothesis that OBT076 will induce immune infiltrate that could restore sentivity to PD-1 targeting.

开始日期2023-11-29

申办/合作机构-

CTIS2023-503270-20-00

/ Completed临床1期IIT

Randomized, non-comparative, open-label early phase Ib study with OBT076 or OBT076 followed by Balstilimab in patients with Adenoid Cystic Carninoma of the Head and Neck

开始日期2023-11-29

申办/合作机构-

NCT04064359

/ Recruiting临床1期

A Phase I, Open-label, Dose Finding Study to Assess the Safety, Tolerability, PK, and Preliminary Efficacy of OBT076, a CD205-directed ADC, in Recurrent and/or Metastatic CD205+ Solid Tumors

The purpose of this study is to evaluate OBT076, which is a drug that combines an antibody with an anti-cancer drug. This class of drugs are called Antibody-Drug Conjugates (ADC). Antibodies are normally produced in the human body by the immune system to fight infections but can be designed to target cancer cells and deliver an anti-cancer drug. OBT076 is composed of an antibody that targets the CD205 protein on cancer cells and delivers an anti-cancer drug which can kill them. OBT076 is an "Investigational Drug", which means that it is still being studied and has not yet been approved by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory authorities to be prescribed by doctors for the treatment of metastatic or recurrent solid tumors. The use of OBT076 in this study is investigational.
This is a Phase I research study designed to look at several dose levels of the study drug to find the highest dose level that is safe and well-tolerated (does not cause unacceptable side effects), and to examine the effects of the study drug in a small group of research participants. The study will also look at the effectiveness of OBT076 as an anti-cancer therapy. Once the optimal dose is determined and safety is assessed, additional research participants will be treated at the optimal dose level to further evaluate safety and effectiveness.

开始日期2019-07-25

申办/合作机构

Oxford BioTherapeutics Ltd.

100 项与 MEN-1309 相关的临床结果

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100 项与 MEN-1309 相关的转化医学

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100 项与 MEN-1309 相关的专利（医药）

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项与 MEN-1309 相关的文献（医药）

2019-10-10·ACS medicinal chemistry letters

Peptide-Cleavable Self-immolative Maytansinoid Antibody–Drug Conjugates Designed To Provide Improved Bystander Killing

Article

作者: Salomon, Paulin ; Ponte, Jose F. ; Veale, Karen H. ; Wu, Rui ; Ab, Olga ; Dong, Ling ; Maloney, Erin K. ; Setiady, Yulius ; Bartle, Laura M. ; Widdison, Wayne C. ; Lanieri, Leanne ; Costoplus, Juliet A. ; Qiu, Qifeng ; Chari, Ravi V. J. ; Skaletskaya, Anna ; Kovtun, Yelena V. ; Lai, Kate

A new type of antibody-drug conjugate (ADC) has been prepared that contains a sulfur-bearing maytansinoid attached to an antibody via a highly stable tripeptide linker. Once internalized by cells, proteases in catabolic vesicles cleave the peptide of the ADC's linker causing self-immolation that releases a thiol-bearing metabolite, which is then S-methylated. Conjugates were prepared with peptide linkers containing only alanyl residues, which were all l isomers or had a single d residue in one of the three positions. A d-alanyl residue in the linker did not significantly impair a conjugate's cytotoxicity or bystander killing unless it was directly attached to the immolative moiety. Increasing the number of methylene units in the maytansinoid side chain of a conjugate did not typically affect an ADC's cytotoxicity to targeted cells but did increase bystander killing activity. ADCs with the highest in vitro bystander killing were then evaluated in vivo in mice, where they displayed improved efficacy compared to previously described types of maytansinoid conjugates.

2016-08-01·Molecular cancer therapeutics2区 · 医学

A New Class of Antibody–Drug Conjugates with Potent DNA Alkylating Activity

2区 · 医学

Article

作者: Archer, Katie E. ; Li, Wei ; Lambert, John M. ; Maloney, Erin K. ; Whiteman, Kathleen R. ; Audette, Charlene A. ; Fishkin, Nathan E. ; Miller, Michael L. ; Chari, Ravi V.J. ; Reid, Emily E. ; Pinkas, Jan ; Kovtun, Yelena ; Goldmacher, Victor ; Singh, Rajeeva ; Modafferi, Holly A. ; Wilhelm, Alan ; Mayo, Michele F.

Abstract:

The promise of tumor-selective delivery of cytotoxic agents in the form of antibody–drug conjugates (ADC) has now been realized, evidenced by the approval of two ADCs, both of which incorporate highly cytotoxic tubulin-interacting agents, for cancer therapy. An ongoing challenge remains in identifying potent agents with alternative mechanisms of cell killing that can provide ADCs with high therapeutic indices and favorable tolerability. Here, we describe the development of a new class of potent DNA alkylating agents that meets these objectives. Through chemical design, we changed the mechanism of action of our novel DNA cross-linking agent to a monofunctional DNA alkylator. This modification, coupled with linker optimization, generated ADCs that were well tolerated in mice and demonstrated robust antitumor activity in multiple tumor models at doses 1.5% to 3.5% of maximally tolerated levels. These properties underscore the considerable potential of these purpose-created, unique DNA-interacting conjugates for broadening the clinical application of ADC technology. Mol Cancer Ther; 15(8); 1870–8. ©2016 AACR.

2016-01-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Chemical de-conjugation for investigating the stability of small molecule drugs in antibody-drug conjugates

Article

作者: Gruenhagen, Jason ; Chetwyn, Nik P ; Li, Yi ; Chen, Tao ; Yehl, Peter ; Medley, Colin D ; Su, Dian ; Gu, Christine

Antibody-drug conjugates (ADCs) offer new therapeutic options for advanced cancer patients through precision killing with fewer side effects. The stability and efficacy of ADCs are closely related, emphasizing the urgency and importance of gaining a comprehensive understanding of ADC stability. In this work, a chemical de-conjugation approach was developed to investigate the in-situ stability of the small molecule drug while it is conjugated to the antibody. This method involves chemical-mediated release of the small molecule drug from the ADC and subsequent characterization of the released small molecule drug by HPLC. The feasibility of this technique was demonstrated utilizing a model ADC containing a disulfide linker that is sensitive to the reducing environment within cancer cells. Five reducing agents were screened for use in de-conjugation; tris(2-carboxyethyl) phosphine (TCEP) was selected for further optimization due to its high efficiency and clean impurity profile. The optimized de-conjugation assay was shown to have excellent specificity and precision. More importantly, it was shown to be stability indicating, enabling the identification and quantification of the small molecule drug and its degradation products under different formulation pHs and storage temperatures. In summary, the chemical de-conjugation strategy demonstrated here offers a powerful tool to assess the in-situ stability of small molecule drugs on ADCs and the resulting information will shed light on ADC formulation/process development and storage condition selection.

项与 MEN-1309 相关的新闻（医药）

2026-01-10

·有驾

抗体-药物偶联物的前景与挑战：新型抗癌药物的革命之路

新型ADC药物：抗癌治疗的未来之星 2019年7月2日消息，医麦客eMedClub报道——抗体-药物偶联物（ADC），这一融合了抗体高特异性与细胞毒素高毒性的创新药物形式，正日益成为抗癌治疗领域的新宠。其独特结构包括抗体、细胞毒素及连接物三大部分，不仅展现了新一代抗体技术的卓越成就，更为癌症患者带来了全新的治疗选择。 1.1 ◉ ADC药物的创新结构 ADC药物抗CD205（DEC-205）进展 2019年6月28日，Menarini Ricerche公布了一项临床前研究的重要成果。该研究涉及一种抗体-药物偶联物（ADC），其靶点为CD205（DEC-205），并命名为MEN1309/OBT076。目前，这款ADC药物正处于I期临床开发阶段，其试验结果已发表在《分子癌症治疗学》杂志上。这一进展，标志着ADC药物在抗癌治疗领域又迈出了坚实的一步。 1.2 ◉ MEN1309/OBT076的发展进展研究揭示，MEN1309/OBT076对CD205阳性肿瘤展现出了显著的抗肿瘤效果。CD205，作为一种跨膜糖蛋白，在多种实体瘤中，诸如胰腺癌、膀胱癌以及三阴性乳腺癌（TNBC）内均有高表达。在体外实验中，该ADC药物对上述肿瘤类型均展现出了强大的抗肿瘤功效。不仅如此，体内研究也证实了其有效性，MEN1309/OBT076在TNBC、胰腺癌和膀胱异种移植模型中均展现出了卓越的抗肿瘤效果，甚至在小鼠PDX模型与患者异种移植中，也能产生持久的反应和肿瘤的完全消退。 Menarini Ricerche的临床前和翻译科学部主任Monica Binaschi博士表示：“这些临床前期数据为靶向CD205的MEN1309/OBT076的临床开发提供了有力支持，我们已启动其一期临床研究。”（NCT03403725） MEN1309/OBT076是一种抗体-药物偶联物（ADC），由完全人源化抗体（针对CD205膜蛋白）与DM4毒素组合而成。 1.3 ◉ Menarini的研发实力及未来方向 Grupo Menarini Internacional，这家总部位于意大利的制药巨头，以其36.67亿欧元的营业额和超过17,600名员工在全球制药行业中占据一席之地。公司目前正在研发四种新型肿瘤药物，其中两种为生物药，包括针对CD157的单克隆抗体MEN1112/OBT357以及抗体-药物偶联物MEN1309/OBT076，该药物靶向CD205，融合了DM4毒素的美登素成分。此外，还有两种小分子药物也在研发之列，如双激酶抑制剂FLT3 PIM和SEL24/MEN1703，以及PI3K抑制剂MEN1611，这些药物均有望用于临床治疗多种血液或实体瘤。 2.1 ◉ ADC药物临床转化的复杂性 ADC药物的复杂性相较于单抗更高，因此其临床或上市申请需要更为全面的数据支持。这包括对ADC的完整结构表征、理化试验、生物物理学分析，以及遵循CMC指南的严格要求。这就需要运用多种生物制药研究和分析方法，其用量可能超过单抗数倍。 2.2 ◉ ADC药物研究的未来前景尽管ADC产品在临床前研究中展现出巨大潜力，但进入临床试验后，往往面临进展缓慢或研究中止的风险。其中，毒性和不完整的表征数据是导致失败的两个关键因素。相较于单抗，ADC的IND进程需要走更长的路，但这也为行业带来了更多的创新机会。结语全球范围内，针对CD205的临床试验正在进行中。

抗体药物偶联物临床1期临床结果

2025-12-10

·GlobeNewswire-Health Care

Oxford BioTherapeutics Enters into a Strategic Collaboration with GSK to Discover Novel Targets for Antibody-Based Therapeutics for the Treatment of Cancer

Collaboration leverages OBT's proprietary OGAP®-Verify platform and GSK's drug development expertise to advance multiple selected novel oncology targetsThe agreement - OBT's second high-profile pharma collaboration this year - reflects the strong validation of OGAP®-Verify discovery platform's potential to drive oncology innovationOBT to receive an upfront payment and may be eligible to receive milestone payments, as well as royalties on net sales of products Oxford, UK and San Jose, California, 10th December 2025 – Oxford BioTherapeutics (OBT), a clinical stage oncology company with a pipeline of immuno-oncology (IO) and Antibody Drug Conjugate (ADC)-based therapies, today announced a multi-year, multi-target strategic collaboration with GSK to discover novel potentially first-in-class antibody-based therapeutics for the treatment of cancer. OBT's recently enhanced proprietary OGAP®-Verify discovery platform enables highly sensitive identification of oncology targets with improved attributes for drug development, supporting the creation of differentiated antibody-based therapies. Under the terms of the agreement, targets are identified via the OGAP®-Verify discovery platform and will be validated through a joint research collaboration. Any further research, development and commercialization efforts against these targets will be driven by GSK. As part of the agreement, OBT will receive an undisclosed upfront payment from GSK and is eligible to receive downstream milestone payments as well as royalties on net sales of any resulting products. “We're delighted to expand our network of world-class partners through this collaboration with GSK. This marks our second major collaboration with a leading global pharma this year - a testament to the growing recognition of our proprietary discovery platform, OGAP-Verify's potential to drive meaningful innovation in cancer research,” said Christian Rohlff, PhD, Chief Executive Officer (CEO) of Oxford BioTherapeutics. “T-cell engager therapeutics and antibody-drug conjugates have shown great promise, yet today only a small fraction of cancer patients are currently eligible for these treatments. We're driven by a patient-centric vision and excited to work with GSK to turn these discoveries into potential new treatment options that could reach many more people living with cancer.” “At GSK, we are committed to discovering, developing & delivering novel medicines to patients in need. Our collaboration with Oxford BioTherapeutics enhances our in-house capabilities by integrating a best-in-class proteomics platform for oncology target identification, enabling us to work together to deliver impactful solutions for patients,” said Chris Austin, M.D., Senior Vice President of Research Technologies at GSK. About Oxford BioTherapeutics Oxford BioTherapeutics is a clinical stage oncology company discovering and developing first in class antibody-based therapies designed to fulfil major unmet patient needs in cancer therapy. These include Bispecific Antibodies and Antibody Drug Conjugate (ADC) therapeutics. OBT is dedicated to discovering and validating the next generation of ADC targets for safe and effective medicines. The OGAP-Verify platform's enhanced sensitivity, specificity, and reliability will significantly accelerate biopharma's capabilities to identify and validate human targets with robust scientific support. Our commitment to leveraging OGAP capabilities underscores our dedication to advancing the forefront of cancer therapy development, with three programs originating from this technology now in clinical development in the US and Europe. OBTs IO discovery process provides unique insights into the cancer-immune cell synapse and has identified several novel IO monoclonal and bispecific antibody candidates for cancer therapies. OBT's lead clinical program, OBT076, initiated expansion in a US Clinical Trial in 2021 in patients with advanced or refractory solid tumors, including gastric, bladder, ovarian and lung cancer, where CD205 is overexpressed. Infiltration of tumors by immunosuppressive cells correlates with adverse outcomes (lower progression free and overall survival), suggesting that this process contributes to the progression of several cancers. OBT's pipeline and development capabilities have been validated through multiple strategic partnerships including with Roche, Boehringer Ingelheim and Zymeworks as well as other world leaders in antibody development (such as Amgen, WuXi, Medarex (BMS) and Alere (Abbott)). OBT has a strong oncology focused management team and board with significant experience in developing IO and antibody-based therapies. For more information on Oxford BioTherapeutics, please visit www.oxfordbiotherapeutics.com and follow us on LinkedIn. Partnering:Dr Christian Rohlff, CEOPartnering@oxfordbiotherapeutics.com Media:MEDiSTRAVA Sylvie Berrebi, Sandi Greenwood, Erica HollingsworthE : OBT@medistrava.comT : +44 (0)203 928 6900

引进/卖出免疫疗法

2025-07-03

·GlobeNewswire-Health Care

Oxford BioTherapeutics Announces Third Oncology Drug Candidate from Boehringer Ingelheim Collaboration Selected to Advance into IND-Enabling Studies

Drug candidate is one of several oncology assets approaching or in clinical development, discovered through Oxford BioTherapeutics’ proprietary OGAP®-Verify discovery platform OBT receives milestone payment associated with advance of drug candidate Oxford, UK and San Jose, California, 3 July 2025 – Oxford BioTherapeutics (OBT), a clinical stage oncology company with a pipeline of immuno-oncology (IO) and Antibody Drug Conjugate (ADC)-based therapies, today announced that Boehringer Ingelheim has selected a third drug candidate, which will now advance into IND-enabling studies under their ongoing collaboration. The target, OB33, was identified using OBT’s proprietary OGAP®-Verify discovery platform. As a result of this milestone, OBT will receive a payment from Boehringer. Immuno-oncological therapies have transformed the cancer treatment landscape. They are however only effective in a subset of patients, requiring the identification of novel immunotherapy targets. The collaboration with Oxford BioTherapeutics complements Boehringer Ingelheim’s development of next-generation potentially life-changing cancer immunotherapies with the identification of unique and specific cancer targets. Dr. Christian Rohlff, Chief Executive Officer, said: “We are pleased to see our partnership with Boehringer Ingelheim reach an important preclinical milestone. It reflects the strength of our collaboration and the scientific excellence of our OGAP discovery platform. This achievement reinforces our strategy of partnering with world-class organizations to translate breakthrough science into potential new cancer therapies. We look forward to the next phase of this highly successful partnership and to continuing to work together to develop innovative first-in-class treatments for patients with difficult to treat cancers.” OBT’s recently launched enhanced OGAP®-Verify discovery platform allows for enhanced sensitivity and target selection, addressing key challenges in the design of therapeutic antibodies and diagnostic tools. This has resulted in an increased overall success rate of these novel compounds transitioning into clinical development. Under the multi-year collaboration, OBT has identified targets using the OGAP®-Verify platform, while Boehringer is responsible for the development and commercialization of resulting product candidates. The OBT–Boehringer partnership began in 2013 and has expanded through subsequent agreements in 2020 and 2022 to include additional programs. The collaboration has yielded multiple development-stage assets, with two candidates currently in clinical trials, one compound now in IND enabling studies, and a fourth target recently optioned by Boehringer Ingelheim. *** About Oxford BioTherapeutics Oxford BioTherapeutics is a clinical stage oncology company discovering and developing first in class antibody-based therapies designed to fulfil major unmet patient needs in cancer therapy. These include Bispecific Antibodies and Antibody Drug Conjugate (ADC) therapeutics. OBT is dedicated to discovering and validating the next generation of ADC targets for safe and effective medicines. The OGAP®-Verify platform’s enhanced sensitivity, specificity, and reliability will significantly accelerate biopharma’s capabilities to identify and validate human targets with robust scientific support. Our commitment to leveraging OGAP capabilities underscores our dedication to advancing the forefront of cancer therapy development, with three programs originating from this technology now in clinical development in the US and Europe. OBT’s Immuno-oncology discovery process provides unique insights into the cancer-immune cell synapse and has identified several novel IO monoclonal and bispecific antibody candidates for cancer therapies. OBT's lead clinical program, OBT076, is currently in Phase I clinical trials in patients with advanced or refractory solid tumors, including gastric, bladder, ovarian and lung cancers, where CD205 is overexpressed. OBT’s pipeline and development capabilities have been validated through multiple strategic partnerships including with Roche, Boehringer Ingelheim, ImmunoGen (now part of Abbvie) and Zymeworks as well as other world leaders in antibody development (such as Amgen, WuXi, Medarex (BMS) and Alere (Abbott). OBT has a strong oncology focused management team and board with significant experience in developing IO and antibody-based therapies. For more information on Oxford BioTherapeutics, please visit www.oxfordbiotherapeutics.com and follow us on LinkedIn. Partnering:Dr Christian Rohlff, CEOPartnering@oxfordbiotherapeutics.com Media:MEDiSTRAVA Sylvie Berrebi, Sandi Greenwood, Erica HollingsworthE : OBT@medistrava.comT : +44 (0)203 928 6900

临床1期免疫疗法抗体药物偶联物

100 项与 MEN-1309 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
恶性实体肿瘤	临床1期	美国	Oxford BioTherapeutics Ltd.	2022-11-09
恶性实体肿瘤	临床1期	比利时	Oxford BioTherapeutics Ltd.	2022-11-09
恶性实体肿瘤	临床1期	法国	Oxford BioTherapeutics Ltd.	2022-11-09
恶性实体肿瘤	临床1期	希腊	Oxford BioTherapeutics Ltd.	2022-11-09
恶性实体肿瘤	临床1期	西班牙	Oxford BioTherapeutics Ltd.	2022-11-09
HR阳性乳腺癌	临床1期	美国	Oxford BioTherapeutics Ltd.	2019-07-25
HR阳性乳腺癌	临床1期	比利时	Oxford BioTherapeutics Ltd.	2019-07-25
HR阳性乳腺癌	临床1期	法国	Oxford BioTherapeutics Ltd.	2019-07-25
HR阳性乳腺癌	临床1期	希腊	Oxford BioTherapeutics Ltd.	2019-07-25
HR阳性乳腺癌	临床1期	西班牙	Oxford BioTherapeutics Ltd.	2019-07-25

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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


Phase 1B part C (AACR2025)	临床1期	CD276阳性实体瘤 CD205 positive	20	OBT076	夢壓鹹蓋夢壓築遞襯觸(襯構糧淵鹹遞衊夢網糧) = 夢顧願醖簾鹹簾窪簾製蓋膚齋艱齋範齋鹹鑰襯 (糧廠憲繭選壓鬱繭鏇築 )	不佳	2025-04-28
Phase 1B part B expansion cohort (AACR2025)	临床1期	CD276阳性实体瘤 CD205 positive	51	OBT076 3.0 mg/kg	襯醖構遞窪網醖製壓齋(製襯夢蓋襯糧艱鏇選窪) = 憲築淵夢繭觸繭淵襯遞蓋築鹹鹽淵鬱鏇構糧鑰 (窪繭膚憲糧範膚襯構襯 ) 更多	积极	2025-04-28
NCT04064359 (ASCO2022) 人工标引	临床1期	实体瘤	20	OBT076 1.6 mg/kg	憲夢餘範簾鑰鑰廠顧積(獵築觸蓋醖繭夢製簾顧) = 製廠鏇網廠壓醖醖鹹淵繭壓餘糧蓋憲膚壓膚鹽 (獵醖夢艱餘壓鏇衊顧壓 )	积极	2022-06-02
NCT04064359 (ASCO2022) 人工标引	临床1期	实体瘤	20	OBT076 2.5 mg/kg	憲夢餘範簾鑰鑰廠顧積(獵築觸蓋醖繭夢製簾顧) = 夢網鹹淵艱艱築夢鹽憲繭壓餘糧蓋憲膚壓膚鹽 (獵醖夢艱餘壓鏇衊顧壓 )	积极	2022-06-02