A Phase 1, Open-Label, Dose-Escalation, and Dose-Expansion Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of SRK-181 Alone and in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON)

This is a multi-center, open-label, Phase 1, first-in-human (FIH), dose-escalation, and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SRK-181 administered alone and in combination with anti-PD-(L)1 therapy in adult patients with locally advanced or metastatic solid tumors. The study is divided into 3 treatment parts (Part A1, Part A2, and Part B) and a Long-Term Extension Phase (LTEP).

开始日期2020-04-23

申办/合作机构

Scholar Rock, Inc.

100 项与 SRK-181 相关的临床结果

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100 项与 SRK-181 相关的专利（医药）

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项与 SRK-181 相关的文献（医药）

2022-08-01·Current opinion in obstetrics & gynecology

Adenomyosis and fertility: does adenomyosis impact fertility and does treatment improve outcomes

Review

作者: Morris, Stephanie N ; Zhang, Wenjia ; French, Hannah M ; Isaacson, Keith B ; Movilla, Peter R

Purpose of review:

Adenomyosis has recently been associated with infertility. Relief of bleeding and pain has been demonstrated with medical and surgical therapy. Less is known about reproductive outcomes after treatment.

Recent findings:

Imaging findings during infertility evaluation can be suggestive of adenomyosis without pathologic evaluation. Among women with infertility undergoing assisted reproductive technologies (ART), adenomyosis is associated with lower live birth rates and clinical pregnancy rates. Treatment with gonadotropin releasing hormone (GnRH) modulators prior to frozen embryo transfer may increase the live birth rate and clinical pregnancy rate among women with adenomyosis. Pregnancy has been documented following image-guided adenomyosis ablation; however, the reproductive impact is not well established. Pregnancy following excisional procedures appears to be well tolerated, although may carry a higher risk of uterine rupture compared with pregnancy following myomectomy. It is not clear if ablative therapy or resection increases pregnancy rates.

Summary:

Adenomyosis is associated with lower embryo implantation rates and ongoing pregnancy rates. Adenomyotic changes in the uterus can be seen by ultrasound and MRI. GnRH modulators may be useful for women with adenomyosis undergoing ART. Additional prospective data is warranted to determine the optimal medical or surgical therapy for women with adenomyosis desiring conception.Video abstract Supplementary digital content, http://links.lww.com.libproxy1.nus.edu.sg/COOG/A78.

2022-03-01·BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy3区 · 医学

Tumor in the Crossfire: Inhibiting TGF-β to Enhance Cancer Immunotherapy

3区 · 医学

Review

作者: Tschernia, Nicholas P ; Gulley, James L

Cancer immunotherapy using monoclonal antibodies targeting immune checkpoints has undoubtedly revolutionized the cancer treatment landscape in the last decade. Immune checkpoint inhibitors can elicit long-lasting, previously unheard-of responses in a number of tumor entities. Yet, even in such tumors as metastatic melanoma and non-small cell-lung cancer, in which immune checkpoint inhibition has become the first-line treatment of choice, only a minority of patients will benefit considerably from these treatments. This has been attributed to a number of factors, including an immune-suppressive tumor microenvironment (TME). Using different modalities to break these barriers is of utmost importance to expand the population of patients that benefit from immune checkpoint inhibition. The multifunctional cytokine transforming growth factor-β (TGF-β) has long been recognized as an immune-suppressive factor in the TME. A considerable number of drugs have been developed to target TGF-β, yet most of these have since been discontinued. The combination of anti-TGF-β agents with immune checkpoint inhibitors now has the potential to revive this target as a viable immunomodulatory therapeutic approach. Currently, a limited number of small molecular inhibitor and monoclonal antibody candidates that target TGF-β are in clinical development in combination with the following immune checkpoint inhibitors: SRK 181, an antibody inhibiting the activation of latent TGF-β1; NIS 793, a monoclonal antibody targeting TGF-β; and SHR 1701, a fusion protein consisting of an anti-PD-L1 monoclonal antibody fused with the extracellular domain of human TGF-β receptor II. Several small molecular inhibitors are also in development and are briefly reviewed: LY364947, a pyrazole-based small molecular inhibitor of the serine-threonine kinase activity of TGFβRI; SB-431542, an inhibitor targeting several TGF-β superfamily Type I activin receptor-like kinases as well as TGF-β1-induced nuclear Smad3 localization; and galunisertib, an oral small molecular inhibitor of the TGFβRI kinase. One of the most advanced agents in this area is bintrafusp alfa, a bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II fused to a human IgG1 mAb blocking PD-L1. Bintrafusp alfa is currently in advanced clinical development and as an agent in this space with the most clinical experience, is a focused highlight of this review.

2021-07-01·Clinical and translational science3区 · 医学

Integrating real‐world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women

3区 · 医学

ArticleOA

作者: Gao, Wei ; Chiuve, Stephanie E. ; Shebley, Mohamad ; Mostafa, Nael M. ; Winzenborg, Insa ; Noertersheuser, Peter ; Beck, Denise ; Owens, Charlotte

Abstract:

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real‐world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN‐BMD) were well‐described by a bi‐exponential relationship with first‐order BMD formation (k1) and resorption (k2) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25–maximum 53]) lose 0.6% FN‐BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10‐year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN‐BMD of 0.975 g/cm2 at menopause, associated with a 10‐year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long‐term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.

项与 SRK-181 相关的新闻（医药）

2024-06-09

·药明康德

疾病控制率达100%的免疫联合疗法；使月度发作率下降98%的基因编辑疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 新型口服双重抑制剂TU2218联用PD-1抑制剂pembrolizumab治疗晚期实体瘤患者，在一项1b期临床试验中的疾病控制率（DCR）达100%。 2. 用于治疗遗传性血管水肿（HAE）的在研体内CRISPR基因编辑疗法NTLA-2002早期临床数据亮眼，单次给药后使患者的月度发作率平均下降了98%。 3. 现货型基因疗法PRGN-2012治疗复发性呼吸乳头状瘤病（RRP）患者的1/2期临床试验达到主要终点，有望成为首个获得FDA批准的用于治疗RRP的疗法。 4. 男性无激素避孕药YCT-529完成了1a期临床试验，在临床前研究中，该候选疗法预防小鼠妊娠的有效率为99%，且100%可逆。药明康德内容团队整理 TU2218：公布1b期临床试验的中期数据 TiumBio公司公布了新型口服双重抑制剂TU2218联用PD-1抑制剂pembrolizumab治疗晚期实体瘤患者1b期临床试验的中期结果。TU2218靶向转化生长因子β受体1（TGFR1）和血管内皮生长因子受体2（VEGFR2）。肿瘤微环境中的TGF-ß和VEGF通路会干扰免疫检查点抑制剂的抗肿瘤活性，因此TU2218有望通过抑制这两种通路最大限度地提高免疫疗法的疗效。此次公布的结果显示，5名接受2期推荐剂量（RP2D）TU2218联用pembrolizumab治疗的患者的DCR为100%，其中两名患者达到了部分缓解（PR），3名患者达到了疾病稳定（SD）。所有剂量组中，12名接受联合治疗的患者中有2人达到了PR，6人达到了SD。在这项研究中，TU2218联用pembrolizumab的耐受性良好，没有观察到剂量限制性毒性（DLT），这与之前的单药治疗试验一致。 NTLA-2002：公布1期临床试验的长期数据 Intellia Therapeutics公司宣布其用于治疗遗传性血管水肿的在研疗法NTLA-2002的1期临床试验的长期数据。NTLA-2002是一种体内CRISPR基因编辑候选疗法，通过脂质纳米颗粒（LNP）以mRNA形式递送CRISPR-Cas9基因编辑系统，靶向敲除血浆前激肽释放酶（KLKB1）基因，以永久性降低血浆中激肽释放酶活性，从而防止遗传性血管水肿的发作。此次公布的结果显示，中位随访时间为20.1个月时，单次NTLA-2002治疗让患者的月均疾病发作率平均减少了98%，中度至重度发作平均减少了99%。在测试的每个剂量水平上，HAE发作率均显著减少。单次输注后，患者最长的无发作期超过26个月，并且仍在持续。此外，100%接受NTLA-2002治疗的患者在停止其他预防性治疗后无需再进行预防性治疗。 PRGN-2012：公布1/2期临床试验的新数据 Precigen公司公布了其现货型基因疗法PRGN-2012治疗复发性呼吸乳头状瘤病患者的1/2期临床试验数据。PRGN-2012旨在激发对抗受HPV6或HPV11感染细胞的免疫反应，以治疗RRP。此前，PRGN-2012已获得FDA和欧盟委员会授予的孤儿药资格，还获得了FDA授予的突破性疗法认定。此次公布的结果显示，该1/2期临床试验达到了主要的安全性和疗效终点。中位随访时间为20个月时，51%（18/35）接受PRGN-2012治疗的患者达到了完全缓解（CR），且不再需要进行手术治疗，CR持续时间超过12个月。86%的患者在接受PRGN-2012治疗后的一年内需要进行的手术次数较治疗前一年减少，从治疗前一年的中位次数4次减少到接受治疗后的0次。此外，PRGN-2012显著改善了达到CR患者的Derkay评分（一种用于测量RRP生长程度的量表）和生活质量评分。安全性方面，PRGN-2012的耐受性良好，无DLT，也没有＞2级的治疗相关不良事件。 ▲PRGN-2012的1/2期临床试验结果（图片来源：参考资料[9]）该公司计划在2024年下半年通过加速批准途径提交PRGN-2012的滚动生物制品许可申请（BLA）。新闻稿指出，如果获得批准，PRGN-2012有可能成为首个获得FDA批准用于治疗RRP的疗法。 YCT-529：公布1a期临床试验数据 YourChoice Therapeutics公司公布其男性无激素避孕药YCT-529的1a期临床试验结果。YCT-529是一种视黄酸受体-α（RAR-a）抑制剂，通过阻断RAR-α来阻止睾丸中精子的产生和释放。临床前研究表明，YCT-529在预防小鼠妊娠方面有99%的有效性，且100%可逆。该研究的结果表明，YCT-529是安全的。 C-CAR031：公布1期临床试验的初步数据阿斯利康（AstraZeneca）公布其GPC3靶向CAR-T疗法C-CAR031的最新临床试验结果。GPC3是一种在肝癌中过表达的表面抗原，该蛋白在健康组织中几乎不存在。C-CAR031是一种GPC3靶向的自体CAR-T疗法，这款CAR-T疗法还同时“装备”了TGFβ以抵抗免疫抑制微环境，以增强其效力。此次公布的结果显示，中位随访时间为5.82个月时，22例可评估疗效的GPC3阳性晚期肝细胞癌（HCC）患者的DCR为90.9%，客观缓解率为50.0%，且该疗法的安全性可控。阿斯利康的早期肿瘤学开发负责人Matt Hellmann博士在接受行业媒体STAT采访时表示：“这是首个在肝癌治疗上显示具疗效的CAR-T疗法。这也是GPC3靶点的首次临床验证。” ▲C-CAR031的疗效结果摘要（图片来源：参考资料[1]） CB-010：公布1期临床试验数据 Caribou Biosciences公司公布了其同种异体CAR-T细胞疗法CB-010治疗复发/难治性B细胞非霍奇金淋巴瘤患者的新数据。CB-010利用基因编辑技术生成，除了表达靶向CD19的嵌合抗原受体，还利用基因编辑技术敲除了免疫检查点蛋白PD-1的表达，旨在提高抗肿瘤活性的持久性。截至2024年4月1日的数据，CB-010的疗效和安全性可与已获批的自体CAR-T细胞疗法相媲美。13名部分人类白细胞抗原（HLA）匹配（≥4个等位基因）患者的总缓解率达92%，CR率为46%，中位无进展生存期（PFS）获得改善，为14.4个月。 ▲接受CB-010治疗患者的无进展生存曲线（图片来源：参考资料[4]） ▲接受CB-010治疗患者的疗效结果（图片来源：参考资料[4]） INB-200：公布1期临床试验的新数据 IN8bio公司公布其耐化疗的转基因自体γδ T细胞疗法INB-200用于治疗新确诊的多形性胶质母细胞瘤的积极早期数据。INB-200是一种强大的协同治疗方法，能在患者接受化疗时持续存在，并保持其识别、参与和杀死癌细胞的自然能力。截至2024年5月30日的数据，中位随访时间为11.7个月，92%接受INB-200治疗的可评估患者的中位PFS超过了7个月（即接受标准治疗方案的患者的中位PFS）。一名患有IDH突变神经胶质瘤的患者在接受治疗后的34.9+个月时仍然存活，且疾病没有进展。近期发表的一项IDH抑制剂治疗IDH突变脑胶质瘤患者的临床试验中，对照组患者的中位PFS为11.1个月，试验组患者的中位PFS为28.5个月。安全性方面，在任何队列中均未报告与治疗相关的严重不良事件、DLT、细胞因子释放综合征、输注反应或免疫效应细胞相关神经毒性综合征。 IFx-2.0：公布1b期临床试验数据 TuHURA Biosciences公司公布了其个体化的候选癌症疫苗IFx-2.0治疗对免疫检查点抑制剂（ICI）耐药的晚期Merkel细胞癌（MCC）和皮肤鳞状细胞癌（cSCC）患者的1b期试验的初步结果。该候选疗法旨在克服患者对ICI的原发性耐药。此次公布的结果显示，连续三周每周给药一次IFx-2.0的耐受性良好。5名此前接受ICI治疗后在3.8个月内疾病就发生进展的晚期MCC患者中，有4人在接受IFx-2.0治疗后重新对ICI治疗产生了持久的应答，包括1例CR、1例病理完全缓解（pCR）和两例PR。患者的平均缓解时间为25个月，其中两名患者已分别持续缓解19个月和23个月，并且仍在持续缓解中。 MDNA11：公布1/2期临床试验的新数据 Medicenna Therapeutics公司公布了其下一代长效IL-2超级激动剂MDNA11治疗晚期实体瘤的新临床结果。MDNA11具有优秀的CD122（IL-2受体β）结合作用，而没有CD25（IL-2受体α）亲和力，从而能优先刺激癌症杀伤效应T细胞和NK细胞。此次公布的结果显示，MDNA11的耐受性良好，没有报告DLT和血管渗漏综合征。MDNA11在胰腺癌患者中表现出持久的缓解，1例转移性胰腺导管腺癌患者在基线时存在的所有病灶均完全消退，已维持超过104周，在停止治疗4个月后仍然保持着缓解。一例双检查点抑制剂治疗后进展的黑色素瘤患者的靶病灶在第28周时完全消退，在第44周的扫描时靶病灶仍保持完全消退。目前，该患者仍在接受MDNA11的治疗，非靶病灶也在继续消退。 WTX-124：公布1/1b期临床试验数据 Werewolf Therapeutics公司公布了其条件激活的白介素-2（IL-2）候选疗法WTX-124治疗接受过ICI治疗的局部晚期或转移性实体瘤患者的1/1b期临床试验数据。结果显示，WTX-124在此类患者中具有临床活性，且耐受性良好。截至2024年5月1日的数据，接受WTX-124单药治疗的患者中有1人获得了持久并经过确认的CR，2人达到了PR。获得缓解的患者在治疗的前两个治疗周期内就出现了缓解，并且靶病灶实现了100%的消退。此外，没有发现WTX-124联用pembrolizumab出现新的安全信号。 ▲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] Phase I study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR-T, in patients with advanced hepatocellular carcinoma (HCC). Retrieved June 4, 2024 from https://meetings.asco.org/abstracts-presentations/234377 [2] Virion Therapeutics Reports Positive First-in-human, First-in-class, Phase 1b Immunogenicity Data of VRON-0200, a Novel Checkpoint Modifier for HBV Functional Cure at EASL Congress. Retrieved June 5, 2024, from https://www.prnewswire.com/news-releases/virion-therapeutics-reports-positive-first-in-human-first-in-class-phase-1b-immunogenicity-data-of-vron-0200-a-novel-checkpoint-modifier-for-hbv-functional-cure-at-easl-congress-302161948.html [3] TiumBio Presents Phase 1b Interim Results for TU2218 in Combination with Pembrolizumab at ASCO 2024 Annual Meeting. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/tiumbio-presents-phase-1b-interim-results-for-tu2218-in-combination-with-pembrolizumab-at-asco-2024-annual-meeting-302160236.html [4] Caribou Biosciences Presents Encouraging Clinical Data from CB-010 ANTLER Phase 1 Trial in Second-line LBCL Patients at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/02/2891868/0/en/Caribou-Biosciences-Presents-Encouraging-Clinical-Data-from-CB-010-ANTLER-Phase-1-Trial-in-Second-line-LBCL-Patients-at-the-2024-American-Society-of-Clinical-Oncology-ASCO-Annual-M.html [5] Werewolf Therapeutics to Present Data from Ongoing Phase 1/1b Clinical Trial of WTX-124 as Monotherapy and in Combination with Pembrolizumab in Solid Tumors. Retrieved June 7, 2024, from https://investors.werewolftx.com/news-releases/news-release-details/werewolf-therapeutics-present-data-ongoing-phase-11b-clinical [6] Medicenna To Present Evidence of Durable Single Agent Activity and Potent Immune Effector Response with MDNA11 in the Dose Escalation Portion of Phase 1/2 ABILITY-1 Study at the 10th Annual Oncology Innovation Forum. Retrieved June 7, 2024, from https://ir.medicenna.com/news-releases/news-release-details/medicenna-present-evidence-durable-single-agent-activity-and [7] Intellia Therapeutics Announces Positive Long-Term Data from Ongoing Phase 1 Study of NTLA-2002, an Investigational In Vivo CRISPR Gene Editing Treatment for Hereditary Angioedema (HAE). Retrieved June 3, 2024, from https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-positive-long-term-data-ongoing [8] TuHURA Biosciences and Kintara Therapeutics Announce Positive Results from Phase 1b Trial of IFx-2.0, a Novel Personalized Cancer Vaccine, in Checkpoint Inhibitor Resistant Advanced Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (cSCC). Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/tuhura-biosciences-and-kintara-therapeutics-announce-positive-results-from-phase-1b-trial-of-ifx-2-0--a-novel-personalized-cancer-vaccine-in-checkpoint-inhibitor-resistant-advanced-merkel-cell-carcinoma-mcc-and-cutaneous-squamo-302161301.html [9] Precigen Announces Groundbreaking Pivotal Study Data for PRGN-2012 in Patients with Recurrent Respiratory Papillomatosis in Which More than Half of Patients Achieved Complete Response. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/precigen-announces-groundbreaking-pivotal-study-data-for-prgn-2012-in-patients-with-recurrent-respiratory-papillomatosis-in-which-more-than-half-of-patients-achieved-complete-response-302161493.html [10] YourChoice Therapeutics Completes Phase 1a Clinical Study for First Hormone-Free Male Birth Control Pill. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603886060/en/ [11] IN8bio Presents Progression-Free Survival Update from Phase 1 Study of INB-200 at 2024 American Society of Clinical Oncology Annual Meeting. Retrieved June 7, 2024, from https://investors.in8bio.com/news-releases/news-release-details/in8bio-presents-progression-free-survival-update-phase-1-study [12] 4DMT Presents Positive Interim Data from Phase 1/2 AEROW Clinical Trial of Aerosolized 4D-710 for Modulator-Ineligible/-Intolerant Cystic Fibrosis at 47th European Cystic Fibrosis Conference. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/06/2894575/0/en/4DMT-Presents-Positive-Interim-Data-from-Phase-1-2-AEROW-Clinical-Trial-of-Aerosolized-4D-710-for-Modulator-Ineligible-Intolerant-Cystic-Fibrosis-at-47th-European-Cystic-Fibrosis-C.html [13] Mythic Therapeutics Presents Initial Dose Escalation Data from Ongoing Phase 1 KisMET-01 Study on MYTX-011 at the American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603700748/en [14] Syndax Announces Plans to Advance into Phase 1b Portion of Trial Evaluating Revumenib in Relapsed or Refractory Metastatic MSS CRC. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/syndax-announces-plans-to-advance-into-phase-1b-portion-of-trial-evaluating-revumenib-in-relapsed-or-refractory-metastatic-mss-crc-302165405.html [15] BridgeBio Oncology Therapeutics announces first patient dosed with BBO-8520 in the Ph. 1 ONKORAS-101 trial for KRASG12C NSCLC. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240606977682/en/ [16] Vivet Therapeutics Presents Interim Data from its Phase 1/2 GATEWAY Trial for the Treatment of Wilson Disease at EASL Congress 2024. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/vivet-therapeutics-presents-interim-data-from-its-phase-12-gateway-trial-for-the-treatment-of-wilson-disease-at-easl-congress-2024-302164666.html [17] Altimmune Presents Data at EASL International Liver Congress™ 2024 Supporting the Disease Modifying Potential and Differentiated Therapeutic Profile of Pemvidutide in Metabolic Dysfunction-Associated Steatohepatitis (MASH). Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/6/5/2893731/0/en/Altimmune-Presents-Data-at-EASL-International-Liver-Congress-2024-Supporting-the-Disease-Modifying-Potential-and-Differentiated-Therapeutic-Profile-of-Pemvidutide-in-Metabolic-Dysf.html [18] Quell Therapeutics Advances QEL-001, its Multi-modular Engineered CAR-Treg Cell Therapy, into Efficacy Cohort of LIBERATE Phase 1/2 Trial in Liver Transplant Patients. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/04/2893353/0/en/Quell-Therapeutics-Advances-QEL-001-its-Multi-modular-Engineered-CAR-Treg-Cell-Therapy-into-Efficacy-Cohort-of-LIBERATE-Phase-1-2-Trial-in-Liver-Transplant-Patients.html [19] Surrozen Initiates Dosing of First Patient in Phase 1b Clinical Trial of SZN-043 for Severe Alcohol-Associated Hepatitis. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/04/2893050/0/en/Surrozen-Initiates-Dosing-of-First-Patient-in-Phase-1b-Clinical-Trial-of-SZN-043-for-Severe-Alcohol-Associated-Hepatitis.html [20] Cue Biopharma Presents Updated Data from Phase 1 Trial of CUE-101 in Recurrent/Metastatic HPV+ Head and Neck Cancer at the 2024 ASCO Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/04/2892974/0/en/Cue-Biopharma-Presents-Updated-Data-from-Phase-1-Trial-of-CUE-101-in-Recurrent-Metastatic-HPV-Head-and-Neck-Cancer-at-the-2024-ASCO-Annual-Meeting.html [21] Merus Presents Interim Data on MCLA-145 Monotherapy and in Combination with Pembrolizumab at the 2024 ASCO® Annual Meeting. Retrieved June 7, 2024, from https://ir.merus.nl/news-releases/news-release-details/merus-presents-interim-data-mcla-145-monotherapy-and-combination [22] BlueSphere Bio Announces IND Clearance of its First in Human Candidate and New Cell Therapy Portfolio for High-Risk Leukemia Patients. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892552/0/en/BlueSphere-Bio-Announces-IND-Clearance-of-its-First-in-Human-Candidate-and-New-Cell-Therapy-Portfolio-for-High-Risk-Leukemia-Patients.html [23] Grey Wolf Therapeutics Presents First Clinical Data for GRWD5769, a First-in-Class ERAP1 Inhibitor, at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/grey-wolf-therapeutics-presents-first-clinical-data-for-grwd5769-a-first-in-class-erap1-inhibitor-at-the-2024-american-society-for-clinical-oncology-asco-annual-meeting-302161297.html [24] Puma Biotechnology Announces Presentation of Findings from a Phase I/Ib Study of Alisertib in Advanced EGFR-Mutated Lung Cancer. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603691086/en [25] Cyclacel Pharmaceuticals Reports New Clinical Data at 2024 ASCO Annual Meeting Highlighting Oral Fadraciclib’s Potential as a Precision Medicine for Cancer. Retrieved June 7, 2024, from https://investor.cyclacel.com/news-releases/news-release-details/cyclacel-pharmaceuticals-reports-new-clinical-data-2024-asco [26] Obsidian Therapeutics Announces Additional OBX-115 Safety and Efficacy Data in Oral Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603008329/en [27] Replimune Presents RP1 Data from the IGNYTE anti-PD1 Failed Melanoma Cohort and RP2 Data in Uveal Melanoma at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://ir.replimune.com/news-releases/news-release-details/replimune-presents-rp1-data-ignyte-anti-pd1-failed-melanoma [28] RS Oncology Announces Positive Data from a Phase 1 Clinical Trial of RSO-021, a First-in-Class Therapeutic for Malignant Pleural Mesothelioma. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603559175/en [29] Ascendis Pharma Presents New Data and Updated Results from Phase 1/2 IL-Believe Trial at ASCO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892565/0/en/Ascendis-Pharma-Presents-New-Data-and-Updated-Results-from-Phase-1-2-IL-Believe-Trial-at-ASCO-2024.html [30] Scholar Rock Presents New Data from SRK-181 Phase 1 DRAGON Trial at ASCO 2024 Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603004778/en [31] invoX Pharma Presents Positive Clinical Data from Phase 1 Study of FS222 in Patients with Advanced Solid Tumours at the 2024 American Society of Clinical Oncology Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603068133/en [32] Eledon Presents Updated Data from Ongoing Phase 1b Trial Evaluating Tegoprubart for Prevention of Rejection in Kidney Transplantation. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892558/0/en/Eledon-Presents-Updated-Data-from-Ongoing-Phase-1b-Trial-Evaluating-Tegoprubart-for-Prevention-of-Rejection-in-Kidney-Transplantation.html [33] ImmuneOncia Announces Biomarker Results from Phase 1 Clinical Trial of CD47 Antibody at ASCO. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603017832/en [34] Entera Bio Reports Phase 1 Clinical Data of First-in-Class, Oral PTH(1-34) Peptide Candidate (EB612) for Patients with Hypoparathyroidism at ENDO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892199/0/en/Entera-Bio-Reports-Phase-1-Clinical-Data-of-First-in-Class-Oral-PTH-1-34-Peptide-Candidate-EB612-for-Patients-with-Hypoparathyroidism-at-ENDO-2024.html [35] Enlivex Receives Regulatory Authorization for the Initiation of a Placebo-Controlled Phase I/II Trial Evaluating Allocetra in Up To 46 Patients with Thumb Osteoarthritis. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892206/0/en/Enlivex-Receives-Regulatory-Authorization-for-the-Initiation-of-a-Placebo-Controlled-Phase-I-II-Trial-Evaluating-Allocetra-in-Up-To-46-Patients-with-Thumb-Osteoarthritis.html [36] Indaptus Therapeutics Announces New Positive Data from Ongoing Phase 1 Trial of Decoy20. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892212/0/en/Indaptus-Therapeutics-Announces-New-Positive-Data-from-Ongoing-Phase-1-Trial-of-Decoy20.html [37] Alkermes Presents Data From Phase 1b Study of ALKS 2680 Demonstrating Improved Wakefulness in Patients With Narcolepsy Type 1 at SLEEP 2024. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/alkermes-presents-data-from-phase-1b-study-of-alks-2680-demonstrating-improved-wakefulness-in-patients-with-narcolepsy-type-1-at-sleep-2024-302161336.html [38] IDRx Reports Updated Preliminary Phase 1 Data from Ongoing Phase 1/1b StrateGIST 1 Trial Supporting Best-in-Class Potential for IDRX-42 in Patients with GIST. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240531639390/en [39] Century Therapeutics Presents Interim Results from Phase 1 ELiPSE-1 Study at ASCO 2024 Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892097/0/en/Century-Therapeutics-Presents-Interim-Results-from-Phase-1-ELiPSE-1-Study-at-ASCO-2024-Annual-Meeting.html [40] MediciNova Announces Data from Phase 1b/2a Clinical Trial of MN-166 (ibudilast) in Glioblastoma Patients at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892064/7767/en/MediciNova-Announces-Data-from-Phase-1b-2a-Clinical-Trial-of-MN-166-ibudilast-in-Glioblastoma-Patients-at-the-American-Society-of-Clinical-Oncology-ASCO-Annual-Meeting-2024.html [41] FibroGen Announces FDA Clearance of Investigational New Drug Application for FG-3165, a Galectin-9 Targeting Monoclonal Antibody, for the Treatment of Patients with Solid Tumors. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892568/0/en/FibroGen-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-FG-3165-a-Galectin-9-Targeting-Monoclonal-Antibody-for-the-Treatment-of-Patients-with-Solid-Tumors.html [42] STORM Therapeutics Presented Interim Phase 1 Clinical Data on its METTL3 RNA Methyltransferase Inhibitor STC-15 at ASCO 2024. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/storm-therapeutics-presented-interim-phase-1-clinical-data-on-its-mettl3-rna-methyltransferase-inhibitor-stc-15-at-asco-2024-302160864.html [43] Black Diamond Therapeutics Presents Promising BDTX-1535 Clinical Data in Patients with Recurrent Glioblastoma at 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://investors.blackdiamondtherapeutics.com/news-releases/news-release-details/black-diamond-therapeutics-presents-promising-bdtx-1535-clinical [44] Immunocore reports updated Phase 1 data of brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, in immune checkpoint pre-treated cutaneous melanoma patients at ASCO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/05/31/2891735/0/en/Immunocore-reports-updated-Phase-1-data-of-brenetafusp-IMC-F106C-an-ImmTAC-bispecific-targeting-PRAME-in-immune-checkpoint-pre-treated-cutaneous-melanoma-patients-at-ASCO-2024.html [45] Kymera Therapeutics Presents New Clinical Data from Ongoing Phase 1 Trial of MDM2 Degrader KT-253 at ASCO Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/01/2891812/0/en/Kymera-Therapeutics-Presents-New-Clinical-Data-from-Ongoing-Phase-1-Trial-of-MDM2-Degrader-KT-253-at-ASCO-Annual-Meeting.html [46] Accutar Biotechnology Presents Phase 1 Data of AC699 Monotherapy in Patients with ER+ / HER2- Breast Cancer at ASCO 2024. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240601126229/en [47] Molecular Partners Presents Positive Data From Completed Phase 1 Trial Of MP0317 (FAP X CD40 DARPin) Monotherapy In Patients With Advanced Solid Tumors At ASCO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/01/2891809/0/en/Molecular-Partners-Presents-Positive-Data-From-Completed-Phase-1-Trial-Of-MP0317-FAP-X-CD40-DARPin-Monotherapy-In-Patients-With-Advanced-Solid-Tumors-At-ASCO-2024.html [48] Updated Data from the Phase 1/2 Study of Olomorasib in KRAS G12C-Mutant Advanced Solid Tumors Presented at the 2024 ASCO® Annual Meeting. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/updated-data-from-the-phase-12-study-of-olomorasib-in-kras-g12c-mutant-advanced-solid-tumors-presented-at-the-2024-asco-annual-meeting-302160829.html [49] ALX Oncology Presents First Evorpacept Combination Data with an Antibody-Drug Conjugate from Phase 1 ASPEN-07 Clinical Trial in Patients with Advanced Bladder Cancer. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/02/2891851/0/en/ALX-Oncology-Presents-First-Evorpacept-Combination-Data-with-an-Antibody-Drug-Conjugate-from-Phase-1-ASPEN-07-Clinical-Trial-in-Patients-with-Advanced-Bladder-Cancer.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

临床结果基因疗法免疫疗法临床2期

2024-06-03

·BioSpace

Scholar Rock Presents New Data from SRK-181 Phase 1 DRAGON Trial at ASCO 2024 Annual Meeting

Promising objective response rates (ORR) were observed in multiple tumor types in anti-PD-(L)1 resistant patients Analysis of baseline biomarker data in clear cell renal cell carcinoma (ccRCC) patients reveals a doubling of the ORR highlighting a potential patient selection strategy SRK-181 combination with pembrolizumab was generally well tolerated Company holding conference call to discuss data with Dr. Toni Choueiri on Tuesday, June 4th at 7 a.m. CDT/8 a.m. EST CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, today announced encouraging data from its Phase 1 DRAGON proof-of-concept trial of SRK-181, a selective inhibitor of latent TGFβ1 activation, in combination with pembrolizumab in patients with advanced solid tumors. The results show encouraging responses in heavily pretreated and anti-PD-(L)1 resistant patients across multiple tumor types. Data were shared in an oral presentation during the American Society of Clinical Oncology (ASCO) Annual Meeting on June 3 in Chicago. “These new data from our SRK-181 program show promising response to treatment with SRK-181 across multiple tumor types and represent further evidence of the value of our highly selective TGFβ platform,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer of Scholar Rock. “The anti-tumor activity we observed in heavily pretreated cancer patients, most notably in ccRCC and melanoma gives us confidence that SRK-181 could be part of a treatment strategy to overcome immune checkpoint inhibitor-associated resistance. In addition, our new finding that baseline CD8+ infiltration status and elevated baseline regulatory T-cell levels in ccRCC correspond with the twofold increase in response rate has the potential to inform a patient selection strategy. We are very encouraged by these new data and are committed to engaging with the FDA in an end of Phase 1 meeting, while also continuing to evaluate opportunities to partner this important program.” Safety data continued to show SRK-181 was generally well tolerated Safety data from all cohorts in the dose expansion phase (Part B; n=78 patients; 1500 mg q3w) continued to show SRK-181 was generally well tolerated when used in combination with pembrolizumab. One Grade 4 treatment-related adverse event (AE) of generalized dermatitis exfoliative was observed in one patient. No Grade 5 treatment-related AEs occurred. The only treatment-related serious adverse event related to SRK-181 or pembrolizumab that occurred in at least 2% of patients was pemphigoid. The most common AEs were rash, pruritis, fatigue, and diarrhea. Data presented continues to provide objective evidence of anti-tumor activity Encouraging responses were observed in multiple tumor types, continuing to support proof-of-concept for SRK-181. The response was assessed by principal investigators based on RECIST 1.1 for patients across five cohorts: clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), melanoma (MEL), urothelial carcinoma (UC), and non-small cell lung cancer (NSCLC). A summary of anti-tumor activity is presented in the table below; results for NSCLC (n=11) are not included because no response was observed. Summary of Response Rate in Multiple Tumor Types ccRCC (n=30) HNSCC (n=11) MEL (n=11) UC (n=11) Objective response rate (ORR) 7 (23.3%) 2 (18.2%) 3 (27.3%) 1 (9.1%) Durability of response (DoR); median (range), months 7.7+ (2.5+, 20.9+) 2.2+ (0.1, 4.3+) 4.9 (1.8, 7.1) 12.9 (12.9, 12.9) Biomarker findings continue to support proof of mechanism Tumor infiltration by CD8+ T-cells was measured in multiple tumor types for which paired biopsy samples (i.e., samples before and after treatment for individual patients) were available. The analysis included patients with ccRCC, melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) or urothelial carcinoma (UC). In 6 out of 9 paired biopsies analyzed, the combination of SRK-181 and pembrolizumab was associated with an enhanced proinflammatory microenvironment, with activated CD8+ T-cells in responding patients across multiple cohorts and the number of activated T-cells correlating with tumor shrinkage. New biomarker findings in ccRCC could inform patient selection strategy Notably, the baseline immune contexture unique to ccRCC amongst the cohorts examined has been identified, predictive of clinical response. An analysis in ccRCC patients showed a positive correlation between baseline CD8+ infiltration status and response rate, with an increase in ORR from 23.3 to 40%, and an improvement in median durability of response (mDoR) from 7.7 to 9.3 months if enrollment had been limited to patients whose tumors were infiltrated by CD8+ T-cells at baseline. In addition, an independent analysis showed a positive correlation between elevated regulatory T-cell (Treg) levels in ccRCC patients pre-treatment and response rate, with an increase in ORR from 23.3 to 50% and improvement in mDoR from 7.7 to 9.8 months if enrollment had been limited to patients whose tumors had elevated Treg levels at baseline. Together, these results suggest that baseline CD8+ status and Treg levels should be further investigated as a potential future patient selection strategy, aimed to predict ccRCC patients who are likely to respond to SRK-181 and anti-PD-(L)1 combination therapy. The presentation is available in the Publications & Posters section of Scholar Rock’s website. For conference information, visit . Conference Call Information Scholar Rock will host a conference call on June 4 at 8 a.m. EST that can be accessed from Events and Presentations page of Scholar Rock’s website. Members of Scholar Rock’s executive management team will be joined by Dr. Toni Choueiri, M.D., Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI). The audio of the conference call can be accessed by registering in advance at the following link: About SRK-181 SRK-181 is a selective inhibitor of TGFβ1 activation being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies, in advanced cancer. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest that TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, as well as suppressing T cell activity, thereby inhibiting anti-tumor immunity. SRK-181 specifically targets the latent TGFβ1 isoform in a context-independent manner, designed to enable complete inhibition of TGFβ1 in all compartments within the tumor microenvironment. Scholar Rock believes that SRK-181 has the potential to overcome this immunosuppressive tumor microenvironment and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. Enrollment of the DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) was completed in December 2023, and patients who remain on the study continue to be treated. The trial enrolled patients in multiple proof of concept cohorts conducted in parallel, including urothelial carcinoma (UC), cutaneous melanoma (MEL), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and clear cell renal cell carcinoma (ccRCC). SRK-181 is an investigational product candidate and its efficacy and safety have not been established. SRK-181 has not been approved for any use by the FDA or any other regulatory agency. About Scholar Rock Scholar Rock is a biopharmaceutical company that discovers, develops, and delivers life-changing therapies for people with serious diseases that have high unmet need. As a global leader in the biology of the transforming growth factor beta (TGFβ) superfamily of cell proteins and named for the visual resemblance of a scholar rock to protein structures, the clinical-stage company is focused on advancing innovative treatments where protein growth factors are fundamental. Over the past decade, Scholar Rock has created a pipeline with the potential to advance the standard of care for neuromuscular disease, cardiometabolic disorders, cancer, and other conditions where growth factor-targeted drugs can play a transformational role. Scholar Rock is the only company to show clinical proof of concept for a muscle-targeted treatment in spinal muscular atrophy (SMA). This commitment to unlocking fundamentally different therapeutic approaches is powered by broad application of a proprietary platform, which has developed novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity. By harnessing cutting-edge science in disease spaces that are historically under-addressed through traditional therapies, Scholar Rock works every day to create new possibilities for patients. Learn more about our approach at ScholarRock.com and follow @ScholarRock and on LinkedIn. Availability of Other Information About Scholar Rock Investors and others should note that we communicate with our investors and the public using our company website , including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on Twitter and LinkedIn. The information that we post on our website or on Twitter or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. Scholar Rock® is a registered trademark of Scholar Rock, Inc. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding its growth, strategy, progress and timing of its clinical trials for SRK-181, and indication selection and development timing, including the therapeutic potential, clinical benefits and safety thereof, expectations regarding timing, success and data announcements of current ongoing clinical trials, the ability of any product candidate to perform in humans in a manner consistent with earlier nonclinical, preclinical or clinical trial data, and the potential of its product candidates and proprietary platform. The use of words such as “may,” “might,” “could,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, without limitation, that preclinical and clinical data, including the results from the Phase 1 clinical trial of SRK-181, are not predictive of, may be inconsistent with, or more favorable than, data generated from future or ongoing clinical trials of the same product candidates; Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline; the data generated from Scholar Rock’s nonclinical and preclinical studies and clinical trials; information provided or decisions made by regulatory authorities; competition from third parties that are developing products for similar uses; Scholar Rock’s ability to obtain, maintain and protect its intellectual property; Scholar Rock’s dependence on third parties for development and manufacture of product candidates including, without limitation, to supply any clinical trials; and Scholar Rock’s ability to manage expenses and to obtain additional funding when needed to support its business activities and establish and maintain strategic business alliances and new business initiatives; as well as those risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock’s subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Scholar Rock’s views only as of today and should not be relied upon as representing its views as of any subsequent date. All information in this press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.

临床结果临床1期ASCO会议免疫疗法

2024-06-02

·药明康德

疾病控制率近97%的肺癌联合疗法；有望逆转功能衰退的创新渐冻症疗法进入临床…… | 一周盘点

▎药明康德内容团队编辑本期看点1. 应世生物（InxMed）公布了ifebemtinib联用garsorasib一线治疗携带KRAS G12C突变的非小细胞肺癌（NSCLC）的早期临床试验结果，31例可评估患者的客观缓解率（ORR）达90.3%，疾病控制率（DCR）为96.8%。2. Enterome公司基于肿瘤肽的免疫疗法EO2463联用来那度胺和利妥昔单抗治疗惰性非霍奇金淋巴瘤（NHL），在一项1/2期临床试验中的完全缓解（CR）率达78%。3. 美国FDA批准了N-肉豆蔻酰转移酶（NMT）抑制剂SPG302的IND申请，该疗法具有恢复突触的独特能力，有望逆转肌萎缩性脊髓侧索硬化（ALS）患者的认知、呼吸和运动功能的衰退。药明康德内容团队整理Ifebemtinib：公布1b/2期临床试验数据应世生物公布了其黏着斑激酶（FAK）抑制剂ifebemtinib联用KRAS G12C突变特异性抑制剂garsorasib一线治疗携带KRAS G12C突变的NSCLC的1b/2期临床试验结果。Ifebemtinib是一种高选择性、口服小分子FAK抑制剂，与化疗药物、靶向疗法和免疫疗法具有协同作用。迄今为止，已有600多名患者接受了ifebemtinib治疗，观察到了良好的安全性和耐受性。截至2024年5月10日的数据，共有33名受试者参与了这项研究。在31名可评估的患者中，ORR为90.3%，DCR为96.8%。28例患者达到了部分缓解（PR），其中26人已得到确认，2例患者达到了疾病稳定（SD）。Ifebemtinib与garsorasib联合治疗的总体安全性与ifebemtinib或garsorasib单药治疗一致，大多数治疗相关不良事件为1级或2级。EO2463：公布1/2期临床试验的新数据 Enterome公司公布了其基于肿瘤肽的免疫疗法EO2463单药和与来那度胺和/或利妥昔单抗联用治疗惰性NHL的效果。EO2463由4种模拟B细胞肿瘤相关抗原CD20、CD22，CD37和CD268（BAFF受体）的多肽以及辅助性的UCP2肽组成，能够激活抗肿瘤免疫反应，清除癌变B细胞。此次公布的结果显示，EO2463单药治疗6周后即可观察到有益的临床应答，9例患者中4例（44%）患者的代谢标志物有减少或肿瘤尺寸缩小。接受EO2463联用来那度胺和利妥昔单抗治疗患者的CR率为78%（7/9），包括5例放射学CR。EO2463可迅速扩增靶向OncoMimics多肽和B细胞抗原的特异性记忆CD8 T细胞，从而诱发快速且强力的细胞毒性反应，这种细胞毒性反应目前已维持长达94周。SPG302：IND申请获得FDA许可 Spinogenix公司宣布，美国FDA已经批准了SPG302治疗肌萎缩性脊髓侧索硬化的1/2期临床试验的IND申请。该试验将评估SPG302在ALS患者中的安全性、耐受性、药代动力学（PK）和药效学。SPG302是一种正在被开发用于治疗ALS和其他神经退行性疾病的再生疗法，每日只需服用一次。它具有恢复突触的独特能力，有望逆转患者认知、呼吸和运动功能的衰退。Zelenirstat（PCLX-001）：公布1期临床试验数据 Pacylex Pharmaceuticals公司公布了其NMT抑制剂zelenirstat治疗复发/难治性淋巴瘤和难治性实体瘤的1期剂量递增安全性和耐受性研究的结果。Zelenirstat是一种潜在“first-in-class”的口服小分子NMT抑制剂，目前正在被开发用于治疗白血病、淋巴瘤和实体瘤。在动物模型中，zelenirstat能在体外选择性地杀死癌细胞，并能使血液恶性肿瘤消退，抑制肺癌和乳腺癌的生长。在急性髓系白血病模型中，zelenirstat能杀死白血病干细胞群，并使正常骨髓细胞再生和生长。此次公布的结果显示，接受推荐的2期剂量7名患者的无进展生存期和总生存期明显优于接受较低剂量治疗的17名患者。这些患者的癌症类型不同（5种），57%的患者保持SD或更好的治疗结果≥6个月。在1名结直肠（CRC）癌患者身上观察到了长期的SD，该患者之前接受的6种疗法中的任何一种都只能带来了短期疗效，而在接受了zelenirstat治疗后，癌胚抗原（CEA）和肿瘤体积减少了约50%。此外，zelenirstat的耐受性良好，不良事件主要是胃肠道副作用，其中大部分能够自行消退，无需减少剂量。TTX-MC138：公布0期临床试验的初步数据 TransCode Therapeutics公司公布了其主要治疗候选药物TTX-MC138的0期临床试验的最新初步数据，表明其具有抗肿瘤活性。TTX-MC138旨在抑制促转移RNA——microRNA-10b，它被认为是多种晚期实体瘤转移的主要调节因子。在临床前研究中，TTX-MC138展现出对多种癌症模型的有效性，包括乳腺癌、胰腺癌、卵巢癌、结肠癌、胶质母细胞瘤等等。此次公布的结果显示，TTX-MC138能显著抑制患者血液中的miRNA-10b，miRNA-10b在给药后的24小时内减少了66%。此外，TTX-MC138的耐受性良好，未发现任何不良反应。Dapiglutide：公布早期临床试验的数据 Zealand Pharma公司公布了其胰高血糖素样肽（GLP）1受体/GLP-2受体双激动剂dapiglutide治疗肥胖的最新临床试验结果。Dapiglutide是一种潜在“first-in-class”的长效肽疗法，旨在利用强效GLP-1激动剂的效果来减重，并通过GLP-2的肠道屏障改善功能来解决与低级别炎症相关的并发症。此次公布的结果显示，接受低剂量dapiglutide治疗12周后，患者的体重平均减轻了4.3%。此外，dapiglutide的耐受性良好。此前公布的药代动力学数据显示，4个剂量组的平均半衰期为123-129小时，支持每周一次的给药频率。一项为期13周的1b期试验正在评估更高剂量的dapiglutide，预计将于2024年下半年获得顶线结果。NC410：公布1b期临床试验数据 NextCure公司公布了其LAIR-2融合蛋白NC410联用pembrolizumab的1b期临床试验的数据。结果显示，在37例可评估、未接受过免疫检查点抑制剂（ICI）治疗、微卫星稳定/微卫星不稳定性低（MSS/MSI-L）、没有肝转移的结直肠癌患者中，有2例达到了确认的PR，17例达到了SD，DCR为51%，疾病控制的中位持续时间为5.5个月。在7名可评估的卵巢癌患者中，有3例达到了PR，DCR为43%。其中，1人持续缓解了7.9个月，1人持续缓解了4.1个月，还有1人已持续缓解了5.1个月，并仍在持续缓解中。SRK-181：公布1期临床试验数据 Scholar Rock公司公布了其旨在克服晚期癌症患者对检查点治疗耐药性的单克隆抗体SRK-181的1期临床试验数据。TGFβ1是在许多人类肿瘤类型中表达的主要TGFβ亚型。研究表明，TGFβ1是免疫抑制肿瘤微环境的关键贡献者。SRK-181是一种选择性的潜在TGFβ1激活抑制剂，与抗PD-1/PD-L1疗法联合使用时，有潜力克服检查点治疗耐药问题，同时可能避免其他非选择性TGFβ抑制方法存在的心脏毒性。此次公布的数据显示，在多种癌症类型中观察到SRK-181令人鼓舞的治疗效果，包括透明细胞肾细胞癌、头颈部鳞状细胞癌、黑色素瘤和尿路上皮癌。生物标志物数据显示，SRK-181联用帕博利珠单抗在抗PD-1/PD-L1疗法耐药患者中创造了增强的促炎微环境。此外，SRK-181具有良好的耐受性。BE-101：IND申请获得FDA许可 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。▲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] Affini-T Therapeutics Announces First Patient Dosed in KRAS G12V Phase 1 Program and Presentation of Trial-in-Progress Poster at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528503183/en[2] selectION Announces Initiation of Phase 1b Clinical Trial Evaluating si-544 in Patients with Psoriasis Vulgaris or Psoriatic Arthritis. Retrieved May 31, 2024, from https://selectiontherapeutics.com/selection-announces-initiation-of-phase-1b-clinical-trial-evaluating-si-544-in-patients-with-psoriasis-vulgaris-or-psoriatic-arthritis/[3] SOTIO Announces First Patient Dosed in Phase 1 Clinical Study of SOT201 for Patients with Solid Tumors. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528380813/en[4] HiberCell Announces First Patient Dosed in Phase 1b Clinical Trial, Evaluating HC-7366 in Combination with Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia (AML). Retrieved May 31, 2024, from https://www.globenewswire.com/news-release/2024/05/28/2888943/0/en/HiberCell-Announces-First-Patient-Dosed-in-Phase-1b-Clinical-Trial-Evaluating-HC-7366-in-Combination-with-Venetoclax-and-Azacitidine-for-the-Treatment-of-Acute-Myeloid-Leukemia-AML.html[5] 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[6] Spinogenix Announces FDA Clearance of IND Application for SPG302, a Novel Therapy for the Treatment of ALS. Retrieved May 31, 2024, from https://www.globenewswire.com/en/news-release/2024/05/29/2889788/0/en/Spinogenix-Announces-FDA-Clearance-of-IND-Application-for-SPG302-a-Novel-Therapy-for-the-Treatment-of-ALS.html[7] Full-Life Technologies Announces Clearance from FDA of IND Application for 225Ac-FL-020 for the Treatment of Metastatic Castration-Resistant Prostate Cancer. Retrieved May 31, 2024, from https://www.prnewswire.com/news-releases/full-life-technologies-announces-clearance-from-fda-of-ind-application-for-225ac-fl-020-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer-302156355.html[8] TransCode Therapeutics Reports Positive Data from First-in-Human Clinical Study Using Novel Lead Therapeutic Candidate, TTX-MC138. Retrieved May 31, 2024, from https://www.globenewswire.com/news-release/2024/05/29/2889976/0/en/TransCode-Therapeutics-Reports-Positive-Data-from-First-in-Human-Clinical-Study-Using-Novel-Lead-Therapeutic-Candidate-TTX-MC138.html[9] 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[10] Biohaven Doses First Patient with its Novel Trop-2 Directed Antibody Drug Conjugate (ADC) BHV-1510 in Advanced or Metastatic Epithelial Tumors. Retrieved May 31, 2024, from https://www.prnewswire.com/news-releases/biohaven-doses-first-patient-with-its-novel-trop-2-directed-antibody-drug-conjugate-adc-bhv-1510-in-advanced-or-metastatic-epithelial-tumors-302157427.html[11] Actym Therapeutics Announces IND Clearance for Phase 1 Clinical Trial Investigating Lead Program ACTM-838 in Patients with Solid Tumors. Retrieved May 31, 2024, from https://www.prnewswire.com/news-releases/actym-therapeutics-announces-ind-clearance-for-phase-1-clinical-trial-investigating-lead-program-actm-838-in-patients-with-solid-tumors-302159288.html[12] Strand Therapeutics Announces First Patient Dosed with Programmable mRNA Therapy STX-001 in Phase 1 Trial for Solid Tumors. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240530103588/en/[13] NextCure Presents Phase 1b Data on NC410 and Pembrolizumab Combination at ASCO 2024. Retrieved May 31, 2024, from https://www.globenewswire.com/news-release/2024/05/30/2891119/0/en/NextCure-Presents-Phase-1b-Data-on-NC410-and-Pembrolizumab-Combination-at-ASCO-2024.html[14] Zealand Pharma announces topline results from the mechanistic investigator-led DREAM trial with low doses of GLP-1/GLP-2 receptor dual agonist dapiglutide. Retrieved May 31, 2024, from https://www.zealandpharma.com/media/zealand-news/[15] Enterome Highlights High Complete Response Rate in Clinical Study of EO2463 for Indolent Non-Hodgkin Lymphoma at ASCO 2024. Retrieved May 31, 2024, from https://www.enterome.com/news-events/enterome-highlights-high-complete-response-rate-in-clinical-study-of-eo2463-for-indolent-non-hodgkin-lymphoma-at-asco-2024/[16] Pacylex Pharmaceuticals Reports Zelenirstat Phase 1 Safety and Efficacy Data at ASCO 2024. Retrieved May 31, 2024, from https://www.newsfilecorp.com/release/210409[17] Scholar Rock to Present New Data from SRK-181 Phase 1 DRAGON Trial at the American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528070137/en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

免疫疗法临床申请临床2期临床结果临床1期

100 项与 SRK-181 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
黑色素瘤	临床1期	美国	Scholar Rock, Inc.	2022-01-30
非小细胞肺癌	临床1期	美国	Scholar Rock, Inc.	2022-01-30
尿路上皮癌	临床1期	美国	Scholar Rock, Inc.	2022-01-30
实体瘤	临床1期	韩国	Scholar Rock, Inc.	2020-04-23

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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


NCT04291079 (DRAGON, ASCO2024) 人工标引	临床1期	晚期恶性实体瘤二线 immunohistochemistry \| flow cytometry	72	SRK-181 + pembrolizumab (ccRCC)	鏇鬱醖網網糧襯顧鹹糧(壓淵鹽艱醖襯繭襯窪製) = The most common (TRAE, ≥10%) of any grade were rash (23.6%), pruritus (20.8%), fatigue (19.4%) and diarrhea (12.5%). 壓鏇鹽鬱醖鬱觸製獵鬱 (繭窪網構壓顧窪構夢齋 ) 更多	积极	2024-05-24
				SRK-181 + pembrolizumab (HNSCC)
NCT04291079 (DRAGON, ESMO_TAT2023) 人工标引	临床1期	晚期恶性实体瘤	34	SRK-181 80-3000mg q3w and 2000mg q2w (Part A1)	鏇獵鹹鏇夢鏇憲醖範遞(構衊壓壓窪製淵築餘窪) = 艱淵鏇齋觸淵醖繭壓製選餘鬱鹹顧壓顧膚壓鏇 (鹽醖繭願顧膚壓顧餘淵 ) 更多	积极	2023-03-07
				SRK-181 240-2400mg+ anti-PD-(L)1 (Part A2)	鏇獵鹹鏇夢鏇憲醖範遞(構衊壓壓窪製淵築餘窪) = 鹽蓋簾廠膚製鏇積簾蓋選餘鬱鹹顧壓顧膚壓鏇 (鹽醖繭願顧膚壓顧餘淵 )
NCT04291079 (DRAGON, Biospace) 人工标引	临床1期	实体瘤	29	SRK-181 (monotherapy)	鹽衊鬱築廠膚製範鹹製(築觸選觸鬱淵製艱鹽齋) = 範鹹築構遞糧鏇簾簾鹹構襯繭鬱艱顧蓋範淵願 (顧築選膚壓遞衊醖選獵 ) 更多	积极	2021-11-12
				SRK-181 (combination therapy)	鹽衊鬱築廠膚製範鹹製(築觸選觸鬱淵製艱鹽齋) = 襯膚選鹽鹽蓋鹽製餘顧構襯繭鬱艱顧蓋範淵願 (顧築選膚壓遞衊醖選獵 ) 更多