Budigalimab

New safety and efficacy data in heavily pre-treated patients with metastatic colorectal cancer (CRC), from a Phase 1 study of ABBV-400, a next-generation, potential best-in-class c-Met directed ADC. Data from a first-in-human study of ABBV-706, a potential best-in-class SEZ6 directed ADC, in small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors and high-grade neuroendocrine neoplasms (NENs). Data from the primary analysis of the Phase 2 LUMINOSITY trial evaluating Telisotuzumab vedotin (Teliso-V), a potential first-in-class c-Met directed ADC, in advanced non-small cell lung cancer (NSCLC). NORTH CHICAGO, Ill., May 28, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that new data from its innovative antibody-drug conjugate (ADC) platform will be showcased across three oral presentations at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting (May 31 - June 4, 2024). AbbVie's ADCs are designed to target unique protein biomarkers such as c-Met (MET protein) and SEZ6 (seizure-related homolog 6 protein), which are over-expressed across various tumor types. By utilizing these biomarkers as targets, ADCs are designed to deliver potent cancer cell death-inducing agents called 'payloads' to the tumor. "Building upon our strong commitment to patients and existing leadership in hematological malignancies, we are rapidly advancing a differentiated pipeline in solid tumors," said Daejin Abidoye, M.D., vice president, head of solid tumors, oncology development, AbbVie. "Our ADC platform allows us to utilize selected biomarkers such as c-Met and SEZ6 to induce targeted cancer cell death by delivering potent anti-cancer agents. The data we are presenting at ASCO demonstrate the clinical potential of this approach across a wide range of difficult-to-treat tumors." Data from the dose-escalation and colorectal cancer (CRC) dose-expansion cohort of an ongoing first-in-human Phase 1 study (NCT05029882) of ABBV-400, a potential best-in-class c-Met directed ADC, will be presented in an oral presentation. The preliminary data show that among 122 heavily pre-treated advanced CRC patients, promising antitumor activity was observed at 2.4 and 3.0 mg/kg doses administered once every 3 weeks, with confirmed objective response rate (ORR) of 18% (n=40) and 24% (n=41) respectively in those groups. In patients with higher c-Met expression, ORR was enriched to >35% at doses ≥2.4 mg/kg. The most common Gr≥3 treatment-emergent adverse events (TEAEs) were anemia (35%), neutropenia (7%) and febrile neutropenia (6%). TEAEs leading to discontinuation occurred in 25 (20.5%) patients. Additional data will be presented at the meeting. ABBV-400 is also being evaluated in a Phase 1b basket study (NCT06084481) in advanced solid tumors as a monotherapy and a Phase 2 study (NCT06107413) in second line metastatic CRC in combination with fluorouracil, folinic acid, and bevacizumab. "c-Met overexpression, found in the majority of patients with metastatic CRC, has been reported to be associated with poor prognosis. However, there are no approved therapies specific for c-Met–overexpressing CRCs, making it an attractive cancer biomarker to target," said Manish Sharma, M.D., Co-Director of Clinical Research at START Midwest (Grand Rapids, MI) and Principal Investigator on the ABBV-400 trial. "Results from this Phase 1 study show preliminary evidence of efficacy for ABBV-400 in patients with heavily pre-treated colorectal cancer and are supportive of further exploration of this novel ADC in CRC and other solid tumors". In addition, early data from the monotherapy dose escalation part of a first-in-human study of ABBV-706, a potential best-in-class SEZ6 directed ADC, will be presented at an oral presentation. The data demonstrate that among a total of 48 efficacy-evaluable patients (23 SCLC and 25 NEN), the overall confirmed objective response rate was 43.8%. Within the SCLC group, the confirmed objective response rate was 60.9%. Among all the 53 enrolled patients at the time of data cut-off, the most common ≥3 TEAEs were neutropenia (42%), anemia (42%), and leukopenia (28%). The ongoing study (NCT05599984) is evaluating ABBV-706 as monotherapy or in combination with budigalimab (a programmed cell death 1 inhibitor), carboplatin, or cisplatin, in patients with advanced solid tumors, including SCLC and other NENs. Additional data will be presented at the meeting. Both ABBV-400 and ABBV-706 utilize a novel, AbbVie proprietary topoisomerase 1 inhibitor (Top1i) payload. Top1i is an anticancer agent that induces cell death by interrupting DNA replication. ABBV-400 and ABBV-706 are designed to specifically deliver Top1i to cells expressing c-Met and SEZ6 respectively. AbbVie will also present data from the primary analysis of the Phase 2 LUMINOSITY non-small cell lung cancer (NSCLC) trial evaluating telisotuzumab vedotin (Teliso-V), a potential first-in-class c-Met directed ADC utilizing a microtubule polymerization inhibitor, monomethyl auristatin E (MMAE) payload, in patients with previously treated c-Met-overexpressing, non-squamous, epidermal growth factor receptor (EGFR) wild type, advanced NSCLC. AbbVie previously announced positive topline results from the study in November 2023. Other presentations from AbbVie's ADC platform include safety and efficacy data in an older population (≥ 65) from the Phase 3 MIRASOL trial of mirvetuximab soravtansine (MIRV) vs investigator's choice chemotherapy in patients with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRα) expression, and a retrospective, exploratory pooled analysis characterizing long-term survivors from four clinical trials examining patients with folate receptor alpha-positive recurrent ovarian cancer treated with MIRV monotherapy. Further information on AbbVie clinical trials is available at . Additional details on oral presentations at ASCO are available below: ABOUT ELAHERE® (mirvetuximab soravtansine-gynx) ELAHERE is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells. Patients requiring access support may call 1-833-ELAHERE or visit . The Marketing Authorization Application (MAA) for ELAHERE in Europe has been accepted by the European Medicines Agency (EMA). Regulatory submissions for ELAHERE are also under review in multiple other countries. INDICATION ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test. IMPORTANT SAFETY INFORMATION WARNING: OCULAR TOXICITY ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis. Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated. Administer prophylactic artificial tears and ophthalmic topical steroids. Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose. Discontinue ELAHERE for Grade 4 ocular toxicities. WARNINGS and PRECAUTIONS Ocular Disorders ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis. Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%). The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients. Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended. Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider. Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms. Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions. Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ELAHERE. Pneumonitis occurred in 10% of patients treated with ELAHERE, including 1% with Grade 3 events and 1 patient (0.1%) with a Grade 4 event. One patient (0.1%) died due to respiratory failure in the setting of pneumonitis and lung metastases. One patient (0.1%) died due to respiratory failure of unknown etiology. Pneumonitis led to permanent discontinuation of ELAHERE in 3% of patients. Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold ELAHERE for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue ELAHERE in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of ELAHERE with close monitoring. Peripheral Neuropathy (PN) Peripheral neuropathy occurred in 36% of patients with ovarian cancer treated with ELAHERE across clinical trials; 3% of patients experienced Grade 3 peripheral neuropathy. Peripheral neuropathy adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (1%), peripheral motor neuropathy (0.9%), polyneuropathy (0.3%), and peripheral sensorimotor neuropathy (0.1%). Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue ELAHERE based on the severity of PN. Embryo-Fetal Toxicity Based on its mechanism of action, ELAHERE can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ELAHERE and for 7 months after the last dose. ADVERSE REACTIONS The most common (≥20 %) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils. DRUG INTERACTIONS DM4 is a CYP3A4 substrate. Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors. USE IN SPECIAL POPULATIONS Lactation Advise women not to breastfeed during treatment with ELAHERE and for 1 month after the last dose. Hepatic Impairment Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN). Please see full Prescribing Information, including BOXED WARNING About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, bi-specific antibody and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. Today, our expansive oncology portfolio comprises of approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit . About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube. Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. SOURCE AbbVie

关注并星标CPHI制药在线日前，艾伯维「Livmoniplimab 注射液」在国内获得临床试验默示许可，用于治疗肝细胞癌。       Livmoniplimab(ABBV-151/ARGX-115)一款人源化抗GARP(LRRC32)/TGFβ1单抗，最早由Argenx公司与比利时天主教鲁汶大学Duve研究所合作开发，其利用Argenx特有的SIMPLE Antibody技术平台，通过以GARP为靶点，阻止抑制免疫系统攻击恶性肿瘤细胞的转化生长因子-β（TGF-β）的产生。       2016年4月，艾伯维与Argenx公司就Livmoniplimab达成合作协议，交易总额6.85亿美元。2018年8月，艾伯维获得该药的独家许可。       目前，Livmoniplimab被开发联合PD-1抑制剂Budigalimab治疗肝细胞癌、NSCLC等晚期/进展性实体瘤，其中Livmoniplimab+Budigalimab+化疗治疗NSCLC的临床试验已进入3期阶段。       关于GARP/TGF-β1及其靶点进展       GARP（糖蛋白A主导重复序列）是Lrrc32基因编码的一个分子量为72 kDa的I型跨膜蛋白，由662个氨基酸组成。GARP是潜伏性转化生长因子-β1（LTGF-β1）的对接受体，在调节性T淋巴细胞（Tregs）、活化的B细胞和血小板上大量表达。而且，研究发现许多预后不良的癌症都出现GARP表达增加。       GARP是TGF-β1表达和激活的关键调节因子，其通过与LTGF-β1结合，将LTGF-β1集中在细胞表面并增强其活性。在细胞表面，GARP与LTGF-β1复合物与整合素（αVβ6和αVβ8）结合，释放活性TGF-β1。而TGF-β1是一种多效性细胞因子，在细胞增殖、发育、凋亡、纤维化、血管生成、伤口愈合和癌症等生物学过程中发挥重要作用。       GARP/TGF-β1是Treg细胞具有免疫抑制功能的核心机理之一。研究发现，GARP通过调节固有和适应性免疫系统支持TGF-β1驱动的癌细胞生长和扩散，并有利于肿瘤免疫逃避。活性TGF-β1通过直接抑制CD8+细胞毒性T细胞（CTL）的克隆扩增和细胞毒性，损害适应性抗肿瘤免疫。       GARP/TGF-β1被认为是肿瘤治疗的潜力靶点，目前全球药企针对该靶点已有几款药物进入临床试验阶段，详见下表。整体来看，在研GARP/TGF-β1靶向药相对较少，且大多处于早期临床，此外，BMS、先声药业在该领域也有布局，但相关药物处于临床前阶段。       资料来源：公开资料       具体品种上，第一三共的DS-1055a是一种具有增强 ADCC 活性的人源化抗GARP单抗，其通过消耗活化的GARP阳性Treg 细胞显示增强的抗肿瘤免疫力，目前正在实体瘤患者中开展1期临床试验。       济民可信的JYB1907是其自主研发的一款GARP/TGF-β1靶向重组人源化单抗，通过特异性结合GARP/TGF-β1，阻断GARP介导的TGF-β1的释放，逆转肿瘤微环境中的免疫抑制效应，提高抗肿瘤免疫应答。       临床前研究显示JYB1907具有良好的安全性和有效性：在多种人肿瘤细胞PBMC人源化肿瘤动物模型中，JYB1907表现出不同程度的肿瘤生长抑制作用，其中在ZR-75-1人乳腺癌模型中可观察到超过一半比例的小鼠肿瘤完全消退。此外，JYB1907联合抗PD-L1抗体在A375人黑色素瘤模型中诱导了部分小鼠的肿瘤完全消退，显著优于抗PD-L1抗体单用的抑瘤效果。2023年1月，JYB1907在美国获批临床，2023年6月在国内获批临床。       HLX60是复星医药自主研发的创新型抗GARP单抗，通过与GARP结合，特异性阻断GARP介导的TGF-β1的释放，从而解除TGF-β1形成的免疫抑制，提高抗肿瘤免疫应答。而且，HLX60还可以通过抗体依赖细胞介导的细胞毒作用清除GARP阳性肿瘤细胞和Tregs等免疫抑制性细胞，从而发挥抗肿瘤作用。       临床前研究结果显示：HLX60与斯鲁利单抗(PD-1单抗)联用的抗肿瘤效果明显优于斯鲁利单抗或HLX60的单药治疗效果。2022年8月，该药联合斯鲁利单抗治疗晚期/转移性实体瘤的1期临床试验在澳大利亚获批开展。2022年10月，该药在国内获批临床，用于治疗实体瘤和淋巴瘤。       总结       整体来看，GARP/TGF-β1赛道处于早期研发阶段，但其潜力不可小觑。2020年Nature上发表的标题为《选择性抑制GARP表达的Tregs产生的TGF-β1克服了癌症患者对PD-1/PD-L1阻断的耐药性》的文章表明，抗GARP-TGF-β1单抗可以作为一种免疫疗法，通过选择性阻断Treg产生TGF-β1诱导肿瘤消退。目前，GARP靶向药除被开发作为单药疗法，还有望成为PD-1/PD-L1单药的新搭档。【智药研习社近期会议预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~