To find a recommended dose of HC-7366 that can be given in combination with azacitidine and venetoclax to patients with AML. The safety and effects of this drug combination will also be studied.

开始日期2024-05-20

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT06234605 / Recruiting临床1期

A Phase 1b, Open-Label, Safety, Tolerability, and Efficacy Study of HC- 7366 in Combination With Belzutifan (WELIREG™) in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

This is a Phase 1b, open-label, multicenter, safety, tolerability and efficacy study of HC-7366 in combination with belzutifan (WELIREG™). This is a multipart study that consists of a HC-7366 monotherapy cohort, a combination dose escalation, and a combination dose expansion. Approximately 80 patients will be enrolled in this study (up to 20 patients will be enrolled into the HC-7366 monotherapy cohort, up to 30 patients into the combination dose escalation, and up to 30 patients into the combination dose expansion). The primary purpose of this study is to determine the maximum tolerated dose of HC-7366 in combination with belzutifan in patients with locally advanced (inoperable) or metastatic RCC with predominantly clear cell histology, irrespective of VHL gene mutation status.

开始日期2024-04-29

申办/合作机构

Hibercell, Inc.初创企业

[+1]

NCT05121948 / Terminated临床1期

A Multicenter, Open-label, Phase 1a/b Study of HC-7366 in Subjects With Advanced Solid Tumors

This is a first in human, multicenter, open label, Phase 1a and 1b dose-escalation and dose-expansion study to establish the maximum tolerated dose, recommended Phase 2 dose, and evaluate the safety and tolerability of QD oral dosing of HC 7366 in a dose escalating fashion in subjects with advanced solid tumors. Up to 40 subjects will be enrolled into the Phase 1a dose-escalation part of the study. The study will be conducted in the United States at approximately 7 to 10 sites. Every effort will be made to ensure approximately 50% of all subjects enrolled into Phase 1a of this study are subjects with the tumors of special interest including squamous cell carcinoma of the head and neck, colorectal cancer, non-small cell lung cancer, and transitional cell carcinoma of the bladder. Subjects with other solid tumor types are also eligible provided study selection criteria are met and they do not exceed 50% of all enrolled subjects. All subjects in Phase 1b will enroll with clear cell renal cell carcinoma. The Phase 1a study will follow a traditional 3+3 design. The starting dose level will be 10 mg QD, escalating to 20, 40, 75, 125, and 150 mg QD as safety allows. All doses are to be administered in the fasting state with water at least 1 hour before food or at least 2 hours after food. The Phase 1b dose-expansion will be at a single dose level of 75 mg based on the safety, tolerability, PK/PD results from Phase 1a to obtain additional safety and preliminary efficacy information. At the discretion of the safety monitoring committee and sponsor, the cohort may be expanded to enroll additional patients and/ or 1-2 additional cohorts will be opened. Up to 30 subjects may be enrolled in the Phase 1b portion of the study at the 75 mg dose. Replacement patients will be enrolled if necessary. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors, discontinuation of treatment for other protocol allowed reason (eg, subject refusal), any other administrative reasons, or after 2 years of treatment, whichever occurs first. For scheduling purposes, dosing in Phase 1a and 1b will occur in 3 week cycles and computed tomography scans will be conducted once every 6 weeks from Cycle 1/Day 1, with the first postbaseline scan after 6 weeks of dosing (precycle 3) until confirmed disease progression, death, start of new anticancer therapy, withdrawal of consent, or end of study, whichever occurs first.

开始日期2022-02-23

申办/合作机构

Hibercell, Inc.初创企业

[+1]

100 项与 HC-7366 相关的临床结果

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100 项与 HC-7366 相关的转化医学

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100 项与 HC-7366 相关的专利（医药）

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项与 HC-7366 相关的文献（医药）

2024-04-11·Journal of medicinal chemistry1区 · 医学

Discovery of HC-7366: An Orally Bioavailable and Efficacious GCN2 Kinase Activator

1区 · 医学

Article

作者: Thomson, Christopher G ; Sood, Sanjeev ; Luo, Diheng ; Lightcap, Eric ; Cheng, Weiwei ; Sherborne, Bradley ; Dudgeon, Crissy ; Wang, Yi ; Rahemtulla, Benjamin F ; Tameire, Feven ; Ramurthy, Savithri ; Pan, Pengwei ; Li, An-Hu ; Taylor, Simon ; Mulvihill, Mark ; Surguladze, David ; Rigby, Alan C ; Wojnarowicz, Paulina ; Xiao, Fenfen ; Du, Hongwen ; Li, Baozhong ; Talbot, Eric P A ; Aicher, Thomas D

A series of activators of GCN2 (general control nonderepressible 2) kinase have been developed, leading to HC-7366, which has entered the clinic as an antitumor therapy. Optimization resulted in improved permeability compared to that of the original indazole hinge binding scaffold, while maintaining potency at GCN2 and selectivity over PERK (protein kinase RNA-like endoplasmic reticulum kinase). The improved ADME properties of this series led to robust in vivo compound exposure in both rats and mice, allowing HC-7366 to be dosed in xenograft models, demonstrating that activation of the GCN2 pathway by this compound leads to tumor growth inhibition.

项与 HC-7366 相关的新闻（医药）

2024-10-23

·BioSpace

HiberCell Receives FDA Fast Track Designation for HC-7366 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML)

BOSTON, Oct. 23, 2024 (GLOBE NEWSWIRE) -- HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics to address advanced cancer and cancer resistance, is pleased to announce that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to HC-7366 for the treatment of adult patients with relapsed or refractory acute myeloid leukemia. The FDA’s Fast Track program aims to facilitate the development, and expedite the review, of novel potential therapies that are designed to treat serious conditions and have the potential to address significant unmet medical need. “We are proud to announce the grant of Fast Track designation by the FDA,” said Jonathan Lanfear, President & CEO of HiberCell. Receiving Fast Track designation highlights the FDA’s recognition of the robust preclinical data generated to date for HC-7366 and the potential for HC-7366 to address the significant unmet need that exists in R/R AML.” Mr. Lanfear continued, “HC-7366 was the first GCN2-activator to enter the clinic in AML and is the only GCN2-targeting agent to receive Fast Track designation for the treatment of AML, validating our preclinical and translational efforts. We plan to leverage the Fast-Track designation to work closely with the FDA to facilitate and, potentially accelerate the development of HC-7366 in AML.” HC-7366 is currently under clinical investigation in both solid and liquid tumor settings. The Phase 1b study in AML (NCT06285890) will evaluate the safety, tolerability, and preliminary efficacy of HC-7366 in relapsed/refractory (R/R) AML or MDS AML. This study aims to determine the recommended Phase 2 dose (RP2D) of HC-7366 in a R/R AML population. Dependent on observations in the dose escalation portion, this study may include additional combination and monotherapy expansions. About HC-7366 HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have antitumor and immunomodulatory activity as a monotherapy and in combination with standard of care agents in both solid and liquid tumor models. HC-7366 is currently under clinical development in a Phase 1b/2 study in clear cell renal cell carcinoma in combination with belzutifan (NCT06234605) and in a Phase 1b study in R/R AML (NCT06285890). About HiberCell HiberCell is a clinical stage oncology company, dedicated to the advancement of first-in-class agents with the novel MOA of modulation of adaptive stress pathways and antitumor immunity. We believe that therapeutic modulation of these mechanisms allows us to address advanced cancer and cancer resistance. Our product candidates HC-5404 and HC-7366, both having completed Phase 1a clinical trials, target the stress response kinases PERK and GCN2, respectively, while our product candidate odetiglucan, currently advancing towards Phase 2 clinical development, modulates the antitumor innate immune response. For more information about HiberCell, please visit hibercell.com. For Media/Investor Inquiries: IR@hibercell.com

临床1期快速通道临床2期

2024-05-29

·GlobeNewswire-Health Care

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)

May 28, 2024 -- HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics to address advanced cancer and cancer resistance, is pleased to announce the first patient dosed in a clinical trial evaluating HC-7366 in combination with standard of care agents venetoclax and azacitidine for advanced acute myeloid leukemia (AML). "We are excited to announce the first patient dosed in this study," said Jonathan Lanfear, President & CEO of HiberCell. "This study builds on the preclinical data we have presented at recent conferences, including the 2023 ASH Annual Meeting and Exposition, which support evaluation of HC-7366 in combination with venetoclax and azacitidine in AML patients with significant unmet need." The study’s principal investigator is Dr. Abhishek Maiti, assistant professor of Leukemia at The University of Texas MD Anderson Cancer Center. Mr. Lanfear continued, "The initiation of this study along with our recently announced study of HC-7366 in clear cell renal cell carcinoma marks the continued advancement of HC-7366 and HiberCell. These are seminal combinatorial studies of HC-7366 with the potential to address large, targeted, and underserved patient populations. We look forward to seeing data for these studies throughout 2024 and 2025." The newly announced Phase 1b study (NCT06285890) will evaluate the safety, tolerability, and preliminary efficacy of HC-7366 in combination with standard dosing of venetoclax and azacitidine in patients with relapsed/refractory (R/R) AML or MDS AML. The study aims to determine the recommended Phase 2 dose (RP2D) of HC-7366 in combination with venetoclax and azacitidine in a R/R AML population. The study will enroll up to 18 patients. HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have antitumor and immunomodulatory activity as a monotherapy and in combination with SOC agents in both solid and liquid tumor models. HC-7366 is currently under clinical development in a Phase 1b/2 study in clear cell renal cell renal cell carcinoma in combination with belzutifan (NCT06234605) and in a Phase 1b study in AML in combination with azacitidine and venetoclax (NCT06285890). HiberCell is a clinical stage oncology company, dedicated to the advancement of first-in-class agents with the novel MOA of modulation of adaptive stress pathways and antitumor immunity. We believe that therapeutic modulation of these mechanisms allows us to address advanced cancer and cancer resistance. Our product candidates HC-5404 and HC-7366, both having completed Phase 1a clinical trials, target the stress response kinases PERK and GCN2, respectively, while our product candidate odetiglucan, currently advancing towards Phase 2 clinical development, modulates the antitumor innate immune response. For more information about HiberCell, please visit hibercell.com. The content above comes from the network. if any infringement, please contact us to modify.

临床研究临床2期

2024-05-02

·GlobeNewswire-Health Care

HiberCell Announces First Patient Dosed in Clinical Collaboration with Merck, Evaluating HC-7366 in Combination with WELIREG® (belzutifan) in patients with advanced ccRCC

May 01, 2024 -- HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics to address cancer relapse, metastasis, and resistance, is pleased to announce the dosing of the first patient in a Phase 1b study evaluating HC-7366, an activator of integrated stress response (ISR) Kinase GCN2, in combination with Merck’s oral hypoxia-inducible factor-2α (HIF-2α) inhibitor WELIREG® (belzutifan) for the treatment of advanced clear cell renal cell carcinoma (ccRCC). The Phase 1b study (NCT06234605) will evaluate the safety, tolerability, and preliminary efficacy of HC-7366 in combination with belzutifan in patients with advanced ccRCC. This trial will also determine a recommended Phase 2 dose (RP2D) of HC-7366 in combination with fixed-dose belzutifan, 120 mg po qd. Dose escalation of HC-7366 in the combination, followed by an expansion phase will optimize dose evaluation. An independent HC-7366 monotherapy cohort is being evaluated in parallel. The study will enroll up to 80 patients at clinical sites across the US. Robert J. Motzer, MD., Section Head, Kidney Cancer, Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center (MSK) will be the lead Principal Investigator (PI) for the clinical trial. "The first patient dosed in this trial marks the beginning of an exciting new chapter in the clinical development of HC-7366," stated Cherry Thomas, M.D., Chief Medical Officer. "The combination of HC-7366 with belzutifan, a key agent for the treatment of clear cell renal cell carcinoma, offers a potentially promising novel and differentiated treatment in a setting with major unmet need and limited treatment options for patients. We recently presented key aspects of the significant preclinical data in support of the combination at the 2024 American Association for Cancer Research Annual Conference." WELIREG® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have antitumor and immunomodulatory activity as a monotherapy and in combination with SOC agents in preclinical models of both solid and liquid tumors. HC-7366 is currently under clinical development in a Phase 1b study in clear cell renal cell carcinoma in combination with belzutifan. HiberCell is a clinical stage oncology company, dedicated to the advancement of first-in-class agents with the novel MOA of modulation of adaptive stress pathways and antitumor immunity. We believe that therapeutic modulation of these mechanisms allows us to address tumor metastasis, treatment resistance, and cancer relapse; all significant drivers of cancer-related deaths. Our product candidates HC-5404 and HC-7366, both having completed Phase 1a clinical trials, target the stress response kinases PERK and GCN2, respectively, while our product candidate odetiglucan, currently advancing towards Phase 2 clinical development, modulates the antitumor innate immune response. For more information about HiberCell, please visit hibercell.com. The content above comes from the network. if any infringement, please contact us to modify.

临床2期AACR会议

100 项与 HC-7366 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性髓性白血病	临床1期	美国	Hibercell, Inc.初创企业	2024-05-20
局部晚期肾细胞癌	临床1期	美国	Hibercell, Inc.初创企业	2024-04-29
晚期恶性实体瘤	临床1期	美国	Hibercell, Inc.初创企业	2022-02-23
结直肠癌	临床1期	美国	Hibercell, Inc.初创企业	2022-02-23
非小细胞肺癌	临床1期	美国	Hibercell, Inc.初创企业	2022-02-23
肾细胞癌	临床1期	美国	Hibercell, Inc.初创企业	2022-02-23
头颈部鳞状细胞癌	临床1期	美国	Hibercell, Inc.初创企业	2022-02-23
膀胱尿路上皮癌	临床1期	美国	Hibercell, Inc.初创企业	2022-02-23
髓系白血病	临床前	-	Hibercell, Inc.初创企业	2023-11-28
晚期头颈部鳞状细胞癌	临床前	美国	Hibercell, Inc.初创企业	2020-07-20

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分期

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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


NCT05121948 (ASH2023)	临床1期	急性髓性白血病	-	HC-7366	製窪範繭艱膚繭獵鑰衊(觸積築鑰膚鑰鑰糧顧簾) = 鏇繭顧廠鏇鹹膚醖觸選醖鑰襯遞襯憲繭顧夢積 (顧鹽鬱壓繭鏇願獵範齋 ) 更多	-	2023-12-10
NCT05121948 (phase 1, AACR_AML and MS2023)	临床1期	急性髓性白血病 GCN2 \| ISR markers such as ATF4 \| ASNS ... 更多	-	HC-7366	醖鬱艱鏇鏇鑰窪憲願夢(選醖網網淵廠膚積製網) = remarkable decrease 遞積鏇積鬱蓋構憲憲廠 (夢壓製膚範網廠簾獵淵 )	积极	2023-05-01