This is a Phase 1/2 study of HST-1011, a CBL-B inhibitor, being developed for the treatment of patients with advanced solid tumors, who relapsed while on or are refractory to approved anti-PD(L)1 therapies or other standard of care.

开始日期2023-03-15

申办/合作机构

HotSpot Therapeutics, Inc.初创企业

100 项与 HST-1011 相关的临床结果

登录后查看更多信息

100 项与 HST-1011 相关的转化医学

登录后查看更多信息

100 项与 HST-1011 相关的专利（医药）

登录后查看更多信息

项与 HST-1011 相关的文献（医药）

2015-04-01·Experimental and therapeutic medicine4区 · 医学

Cbl-b-regulated extracellular signal-regulated kinase signaling is involved in the shikonin-induced apoptosis of lung cancer cells in vitro

4区 · 医学

Article

作者: Zhang, Meng ; Xu, Xiao-Man ; Qu, Dan ; Li, Sheng-Qi ; Zhang, Y I ; Chen, Y U

Shikonin (SK), a naturally occurring naphthoquinone, exhibits antitumor activity. However, its precise mechanisms of action are unknown. In the present study, the effects of SK on NCI-H460 human lung cancer cells were investigated. It was found that SK reduced cell viability and induced apoptosis in the NCI-H460 cells. Additionally, SK inhibited extracellular signal-regulated kinase (ERK) activity, which indicates that inhibition of the ERK pathway is probably one of the mechanisms by which SK induced NCI-H460 cell apoptosis. The expression of Cbl-b was significantly increased by treatment with SK for 4 h, and gradually increased to a maximal level at 24 h; the time taken for the upregulation of Cbl-b protein was in accordance to that required for the downregulation of phospho (p)-ERK protein. The Cbl inhibitor Ps341 reversed the SK-induced downregulation of p-ERK and apoptosis of NCI-H460 cells. These results indicate that Cbl-b potentiates the apoptotic action of SK by inhibiting the ERK pathway in lung cancer cells.

1999-03-11·Oncogene1区 · 医学

cbl-b inhibits epidermal growth factor receptor signaling

1区 · 医学

Article

作者: Mark Frankel ; Maccon M Keane ; Stan Lipkowitz ; Seth A Ettenberg ; Ling-Mei Wang ; Marion M Nau ; Jacalyn H Pierce

The role of cbl-b in signaling by the epidermal growth factor receptor (EGFR) was studied and compared with c-cbl. We demonstrate in vivo, that cbl-b, like c-cbl, is phosphorylated and recruited to the EGFR upon EGF stimulation and both cbl proteins can bind to the Grb2 adaptor protein. To investigate the functional role of cbl proteins in EGFR signaling, we transfected cbl-b or c-cbl into 32D cells overexpressing the EGFR (32D/EGFR). This cell line is absolutely dependent on exogenous IL-3 or EGF for sustained growth. 32D/EGFR cells overexpressing cbl-b showed markedly inhibited growth in EGF compared to c-cbl transfectants and vector controls. This growth inhibition by cbl-b was the result of a dramatic increase in the number of cells undergoing apoptosis. Consistent with this finding, cbl-b overexpression markedly decreased the amplitude and duration of AKT activation upon EGF stimulation compared to either vector controls or c-cbl overexpressing cells. In addition, the duration of EGF mediated MAP kinase and Jun kinase activation in cells overexpressing cbl-b is shortened. These data demonstrate that cbl-b inhibits EGF-induced cell growth and that cbl-b and c-cbl have distinct roles in EGF mediated signaling.

项与 HST-1011 相关的新闻（医药）

2024-11-07

·PRNewswire

HotSpot Therapeutics Presents Additional Phase 1 Biomarker Data on Novel CBL-B Inhibitor HST-1011 at 2024 Society for Immunotherapy of Cancer Annual Meeting

BOSTON, Nov. 7, 2024 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," today announced it will present additional Phase 1 clinical biomarker data for HST-1011, an investigational oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B), in a poster presentation at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting. "These biomarker data emerging from our Phase 1 clinical study of HST-1011 provide strong support for the biological activity and therapeutic potential of CBL-B inhibition, with HST-1011 treatment yielding an increase in immune activation as assessed through both peripheral blood and tumor gene expression," said Alison O'Neill, M.D., Chief Medical Officer of HotSpot Therapeutics. "Moreover, while the data are preliminary and in a small number of patients, baseline immune signature analyses suggest the potential for the prediction of clinical response. Collectively, the insights derived from these data support the further interrogation of biomarkers as HST-1011 advances through future clinical development." The presentation describes additional clinical biomarker data from the ongoing Phase 1 monotherapy dose-escalation study of HST-1011: An HST-1011-derived gene response signature showed a consistent dose-dependent increase in patient peripheral blood, with patients who demonstrated clinical benefit showing a higher expression of the signature in on-treatment biopsies. Preliminary T- and B-cell receptor next-generation sequencing data showed HST-1011 impacted both immune cell populations, with changes observed in several metrics associated with clinical benefit. At baseline, patients who benefitted from HST-1011 treatment showed higher tumor-infiltrating lymphocyte expression and a higher immune signature score, suggesting a potential for prediction of clinical benefit. About HotSpot Therapeutics, Inc. HotSpot Therapeutics, Inc. is a clinical-stage biotechnology company that is pioneering a new class of allosteric drugs that target certain naturally occurring pockets on proteins called "natural hotspots." These pockets are decisive in controlling a protein's cellular function and have significant potential for new drug discovery by enabling the systematic design of potent and selective small molecules with novel pharmacology. The Company's proprietary Smart Allostery™ platform combines computational approaches and AI-driven data mining of large and diverse data sets to uncover hotspots with tailored pharmacology toolkits and bespoke chemistry to drive the rapid discovery of novel hotspot-targeted small molecules. Leveraging this approach, HotSpot is building a broad pipeline of novel allosteric therapies for the treatment of cancer and autoimmune diseases. To learn more, visit . Investor & Media Contact: Natalie Wildenradt [email protected] SOURCE HotSpot Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期免疫疗法AACR会议

2024-11-07

·PRNewswire

Florida Cancer Specialists & Research Institute Physicians Advancing Breakthroughs in Cancer Immunotherapy

Studies Selected for Presentation at Global Gathering FORT MYERS, Fla., Nov. 7, 2024 /PRNewswire/ -- Clinical research conducted with participation from Florida Cancer Specialists & Research Institute, LLC (FCS) continues to advance science and breakthroughs in cancer immunotherapy, which uses the body's immune system to find, target and fight many forms of the disease. FCS physician investigators are co-authors of research results being presented this week at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Houston, the largest cancer immunotherapy conference of international leaders in the field. Continue Reading FCS physician investigators are co-authoring research being presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Houston, the world’s largest gathering of leaders in immunotherapy research. FCS President & Managing Physician Lucio N. Gordan, MD said, "Our shared aim is to make immunotherapy a standard of care to improve outcomes for cancer patients. Each discovery achieved through our robust clinical trials research program is bringing us closer to that reality." The following FCS physician investigators are co-authors of research results being presented during oral and/or poster abstract presentations: FCS Director of Drug Development Manish Patel, MD: Phase 1B/2, multicenter dose escalation and expansion of muzstotug (ADG126, a masked anti-CTLA-4 SAFEbody®) in combination with Pembrolizumab in advanced/metastatic MSS CRC (abstract #744); Noted as a "Top 100" Evaluation of immunomodulatory effects of ifinatamab deruxtecan (I-DXd) in the IDeate-Pantumor01 phase 1/2 study in patients with advanced solid tumors (abstract #629) A phase 1/2 clinical trial of anti-VISTA KVA12123 alone and in combination with Pembrolizumab in patients with advanced solid tumors (abstract #625) Triple blockade of DNAM-1 axis with COM701 (anti-PVRIG) + COM902 (anti-TIGIT) + pembrolizumab shows preliminary antitumor activity in patients with platinum resistant ovarian cancer, interim results of a phase I trial (abstract #985) Peripheral Blood and Tumor Gene Expression as Biomarkers and Potential Predictors of Clinical Outcome with HST-1011, an Oral CBL-B inhibitor (abstract #1310) Director of Drug Development, Lake Nona DDU Cesar Perez, MD – the late-breaking abstract: Phase 1 study of XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, in combination with atezolizumab in patients with advanced solid tumors (abstract #1455) Alexander Philipovskiy, MD, PhD – Abequolixron (RGX-104), a first-in-class oral immunotherapy targeting the liver-X receptor (LXR), in combination with docetaxel in recurrent advanced/metastatic non-small cell lung cancer (NSCLC) (abstract #657). FCS Associate Director of Drug Development Judy Wang, MD: CONSORTIUM-IO: A phase 1 study evaluating a combination of an 11-strain bacterial consortium (VE800) and Nivolumab in treatment of select refractory or metastatic cancers (abstract #607); Noted as a "Top 100" Pharmacodynamic activities of the anti-MICA/B monoclonal antibody CLN-619, evaluated as a monotherapy, support the proposed mechanisms of action and correlate with response (abstract #195) "Immunotherapy clinical trials continue to play a large role in oncology drug development," notes Dr. Manish Patel. "In ongoing studies conducted at our three drug development units, we continue to uncover critical new information about the body's response to immunotherapy, which is improving effectiveness and offering new hope for cancer patients worldwide." As one of the largest clinical research programs in the country, FCS provides access to more than 300 clinical trials at any given time within its 32 late-phase designated FCS clinics and three Drug Development Units, where research is conducted on new treatments when they are first developed, prior to FDA approval. In fact, the majority of new cancer drugs approved for use in the U.S. have been studied in clinical trials with FCS participation. Learn more about clinical trials and advance research conducted a FCS here: . About Florida Cancer Specialists & Research Institute, LLC: (FLCancer.com) Florida Cancer Specialists & Research Institute (FCS) offers patients access to more clinical trials than any private oncology practice in Florida. The majority of new cancer drugs recently approved for use in the U.S. were studied in clinical trials with FCS participation.* Recognized for our research, FCS is a recipient of the national Clinical Trials Participation Award presented by the American Society of Clinical Oncology (ASCO). FCS physicians, trained in prestigious medical schools and research institutes, are consistently ranked nationally as Top Doctors by U.S. News & World Report. Celebrating its 40th year in 2024, FCS has built a national reputation for excellence that is reflected in exceptional and compassionate patient care, driven by innovative clinical research, cutting-edge technologies and advanced treatments, including targeted therapies genomic-based treatment and immunotherapy. Our highest values are embodied by our outstanding team of highly trained and dedicated physicians, clinicians and staff. *Prior to approval SOURCE Florida Cancer Specialists & Research Institute WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

免疫疗法临床1期ASCO会议

2024-10-04

·PRNewswire

HotSpot Therapeutics to Present Additional Phase 1 Biomarker Data on Novel CBL-B Inhibitor HST-1011 at 2024 Society for Immunotherapy of Cancer Annual Meeting

BOSTON, Oct. 4, 2024 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," today announced it will present additional Phase 1 clinical biomarker data for HST-1011, an investigational oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B), in a poster presentation at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting, taking place November 6-10, 2024, in Houston, Texas. The poster will showcase exploration of potential clinical biomarkers that correlate with signs of clinical activity in patients from the ongoing Phase 1 monotherapy dose-escalation study of HST-1011. Presentation details are as follows: Title: Peripheral Blood and Tumor Gene Expression as Biomarkers and Potential Predictors of Clinical Outcome with HST-1011, an Oral CBL-B Inhibitor Session Date and Time: Sat., Nov. 9, 2024, 9:00 AM-8:30 PM CT Location: Exhibit Halls A & B, George R. Brown Convention Center Abstract Number: 1310 About HotSpot Therapeutics, Inc. HotSpot Therapeutics, Inc. is a clinical-stage biotechnology company that is pioneering a new class of allosteric drugs that target certain naturally occurring pockets on proteins called "natural hotspots." These pockets are decisive in controlling a protein's cellular function and have significant potential for new drug discovery by enabling the systematic design of potent and selective small molecules with novel pharmacology. The Company's proprietary Smart Allostery™ platform combines computational approaches and AI-driven data mining of large and diverse data sets to uncover hotspots with tailored pharmacology toolkits and bespoke chemistry to drive the rapid discovery of novel hotspot-targeted small molecules. Leveraging this approach, HotSpot is building a broad pipeline of novel allosteric therapies for the treatment of cancer and autoimmune diseases. To learn more, visit . Investor & Media Contact: Natalie Wildenradt [email protected] SOURCE HotSpot Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

免疫疗法临床1期AACR会议

100 项与 HST-1011 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床2期	美国	HotSpot Therapeutics, Inc.初创企业	2023-03-15
复发癌	临床2期	美国	HotSpot Therapeutics, Inc.初创企业	2023-03-15
难治性癌症	临床2期	美国	HotSpot Therapeutics, Inc.初创企业	2023-03-15
B细胞淋巴瘤	临床1期	美国	HotSpot Therapeutics, Inc.初创企业	-
肿瘤	临床前	-	HotSpot Therapeutics, Inc.初创企业	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


PRNewswire 人工标引	N/A	实体瘤	-	HST-1011	願鏇淵選繭蓋選夢獵遞(鹽構鬱簾淵願醖範築繭) = patients who benefitted from HST-1011 treatment showed higher tumor-infiltrating lymphocyte expression and a higher immune signature score, suggesting a potential for prediction of clinical benefit. 鑰夢築網膚顧艱選憲鏇 (衊構壓糧襯鹽願選膚鏇 )	积极	2024-11-07