A Multicenter, Open-Label, Phase Ⅱ Clinical Trial to Evaluate the Safety and Efficacy of TTAC-0001, a Fully Human Monoclonal Antibody in Patients With Recurrent Glioblastoma Progressed on Bevacizumab Including Therapy

This is a phase II, open-Label clinical trial to evaluate the safety and efficacy of TTAC-0001 in patients with recurrent glioblastoma who was progressed on bevacizumab including therapy.

开始日期2019-11-13

申办/合作机构

PharmAbcine Inc.

NCT03722342

/ Unknown status临床1期

A Phase 1b, Open-Label, Safety and Tolerability Study of TTAC-0001 in Combination With Pembrolizumab in Patients With Recurrent Glioblastoma

This is a phase 1b, open-Label clinical trial to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of TTAC-0001 administered in combination with pembrolizumab in patients with recurrent glioblastoma.

开始日期2019-01-16

申办/合作机构

PharmAbcine Inc.

100 项与奥伐西单抗相关的临床结果

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100 项与奥伐西单抗相关的专利（医药）

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项与奥伐西单抗相关的文献（医药）

2020-07-01·Journal of biomolecular NMR3区 · 生物学

NMR mapping of the highly flexible regions of 13C/15N-labeled antibody TTAC-0001-Fab

3区 · 生物学

Article

作者: Yoo, Jin-San ; Lee, Joon-Hwa ; Choi, Joonhyeok ; Jeong, Jong Geun ; Nam, Ju Ryoung ; Cha, Soyoung ; Kim, Hak-Nam ; Ryu, Kyoung-Seok ; Kim, Jihong ; Lee, Weon Sup

Monoclonal antibody (mAb) drugs are clinically important for the treatment of various diseases. TTAC-0001 is under development as a new anti-cancer antibody drug targeting VEGFR-2. As the less severe toxicity of TTAC-0001 compared to Bevacizumab, likely due to the decreased in vivo half-life, seems to be related to its structural flexibility, it is important to map the exact flexible regions. Although the ¹³C/¹⁵N-labeled protein is required for NMR analyses, it is difficult to obtain antibody fragments (Fab and scFv) containing disulfide bonds through general cytosolic expression in Escherichia coli (E. coli). Here, we notably increased the periplasmic expression of the ¹³C/¹⁵N-labeled TTAC-0001-Fab (¹³C/¹⁵N-TTAC-Fab) through simple isopropyl β-D-1-thiogalactopyranoside (IPTG)-induction at an increased optical density (1.5 OD_600nm). Through NMR triple resonance experiments, two loop insertions (LI-1 between the V_H and C_H1; LI-2 between the V_L and C_L) were confirmed to be highly flexible. The additional LIs could be another way to engineer the antibody by changing the pharmacokinetic properties.

2017-12-01·Investigational new drugs3区 · 医学

Phase I trial and pharmacokinetic study of tanibirumab, a fully human monoclonal antibody to vascular endothelial growth factor receptor 2, in patients with refractory solid tumors

3区 · 医学

Article

作者: Sun, Jong-Mu ; Kang, Won Ki ; Park, Young Suk ; Lee, Weon Sup ; Park, Se Hoon ; Lee, Seon Young ; Lee, Jeeyun ; Lim, Ho Yeong ; Ahn, Myung-Ju ; Park, Joon Oh ; Lee, Su Jin ; Yoo, Jin San

Summary:

Background Tanibirumab is a fully human monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a first-in-human phase I study of tanibirumab in patients with solid tumors refractory to standard chemotherapy. Primary endpoints were evaluating safety, pharmacokinetics (PKs), estimating maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). Methods We designed our study to escalate tanibirumab at 9 different dose levels with a 3 + 3 method and tanibirumab (1–28 mg/kg) was administered intravenously on D1, 8, 15 in 28-day courses. Dose limiting toxicities (DLTs) were only assessed during the first cycle of treatment and response evaluation was performed every 2 cycles. The effects of tanibirumab on several angiogenic factors were analyzed. Results From October 2011 to September 2013, a total of 26 patients with refractory solid tumors were enrolled. The median age was 58 years (range, 27–75) and 20 patients were male. The most common tumor type was colorectal cancer (N = 19) and seven patients had a history of previous bevacizumab treatment. As hemangioma continued to occur, the final dose level, 28 mg/kg, was not performed. DLTs were not found, and the MTD was confirmed to be 24 mg/kg. Hemangioma was observed in 16 patients (61.5%), but all were grade 1–2 and disappeared after discontinuation of the study drug. Among the 18 patients in the efficacy set, no objective response was observed, but 11 patients showed stable disease. PKs were characterized by dose-dependent linear exposure and the mean trough concentrations exceeded biologically relevant target levels at 12 mg/kg and above. Serum VEGF, soluble VEGFR-2, and PlGF increased at the 4 mg/kg dose level and above. Conclusions Treatment with tanibirumab showed a tolerable toxicity profile and modest clinical efficacy in patients with refractory solid tumors. A phase II trial of tanibirumab is ongoing now.

2016-05-03·Expert opinion on investigational drugs2区 · 医学

Novel anti-angiogenic therapeutic strategies in colorectal cancer

2区 · 医学

Review

作者: Tampellini, M ; Scagliotti, G V ; Sonetto, C

INTRODUCTION:

Anti-angiogenetic agents are currently the standard of care in metastatic CRC patients. Bevacizumab, aflibercept, regorafenib and recently ramucirumab have significantly improved both progression-free and overall survival in different lines of treatment. Since bevacizumab's approval, a number of novel anti-VEGF agents have been tested in preclinical and clinical models.

AREAS COVERED:

This review is focused on the most recent clinical results of novel agents targeting VEGF and its receptors with a major focus on those investigated recently in clinical trials.

EXPERT OPINION:

In the last 15 years, a number of new anti-angiogenetic agents have been tested. Unfortunately, most of them have demonstrated unacceptable toxicities or failed to show activity. When tested as single agents, encouraging preliminary results were reported with fruquintinib, famitinib, and nintedanib. Interesting novel mechanisms of action are also being explored: VGX-100 is a monoclonal antibody (mAb) which binds to VEGF-C, inhibiting activation of VEGFR-2 and VEGFR-3 when combined with bevacizumab; tanibirumab is a mAb which binds to VEGFR-2 and vanucizumab is a bispecific mAb binding both to VEGF-A and Angiopoietin-2. Data about the combination of these agents with chemotherapy are very encouraging, even though preliminary. However, the definition of specific predictive biomarkers remains a priority.

项与奥伐西单抗相关的新闻（医药）

2024-10-15

·PRNewswire

PharmAbcine Announces Safety Approval for 4mg Single-dose Cohort in Phase 1 Clinical Trial of PMC-403 for Neovascular Age-related Macular Degeneration

Safety Review Committee (SRC) approves single ascending dose 4mg cohort in Phase 1 trial of PMC-403, preparing for multiple ascending dose 4 mg cohort. PMC-403 is being explored in broader therapeutic areas, including rare vascular disease systemic capillary leak syndrome (SCLS) and kidney diseases. DAEJEON, South Korea, Oct. 14, 2024 /PRNewswire/ -- PharmAbcine, Inc. (KOSDAQ: 208340), a clinical-stage public company developing next-generation therapeutics to address unmet medical needs, today announced that its TIE2-activating antibody candidate, PMC-403, has received unanimous safety approval from the Safety Review Committee (SRC) for the 4mg single ascending dose (SAD) cohort in its Phase 1 clinical trial for neovascular age-related macular degeneration (nAMD). The Company is now preparing to begin enrollment for the 4mg multiple ascending dose (MAD) cohort. PMC-403 is a novel TIE2-activating antibody with a unique mechanism that stabilizes pathological, leaky blood vessels. TIE2 receptors, expressed on endothelial cells, play a critical role in vessel normalization processes such as angiogenesis and intercellular adhesion, thereby inhibiting the progression of AMD. This Phase 1 trial targets patients with neovascular AMD who no longer respond to anti-VEGF standard therapies. The safety and tolerability of the 4mg single dose were successfully confirmed, laying the groundwork for advancing to the multiple-dosing phase. Dr. Weon Sup Lee, Head of R&D and Chief Technology Officer at PharmAbcine, stated, "The successful completion of the 4mg single-dose study is a significant milestone, highlighting the potential of PMC-403 as a breakthrough treatment for AMD. As we move forward with the multiple-dose study, we aim to gather additional safety and efficacy data to establish a robust foundation for Phase 2 trials." Macular degeneration, a leading cause of blindness, results from aging-related damage to the retina, particularly due to the development of abnormal blood vessels in the macula. The global aging population has led to a rapid increase in cases, and current treatments with anti-VEGF inhibitors are often insufficient for complete treatment. Consequently, there is a growing demand for therapies with novel mechanisms of action. PharmAbcine plans to continue its research with the goal of initiating a Phase 2 trial after confirming the safety and efficacy of the 4mg multiple-dose cohort. The Company expects PMC-403 to play a pivotal role in the global market for AMD treatments. Beyond ophthalmology, PMC-403 is being explored in therapeutic areas, including vascular-related rare diseases, Acute Respiratory Distress Syndrome, Inflammatory Bowel Disease, Duchenne Muscular Dystrophy, Traumatic Spinal Cord Injury, oncology and kidney diseases. The Company has collaborated with Dr. Kirk Druey, former Chief of the NIH's Lung and Vascular Inflammation Section, to explore PMC-403's efficacy in animal models for Systemic Capillary Leak Syndrome (SCLS, also known as Clarkson disease). In a recent interview, Dr. Druey expressed excitement about PMC-403's potential in treating SCLS patients. While there is currently no approved treatment for SCLS, PMC-403 received Orphan Drug Designation (ODD) from the U.S. FDA for the treatment of SCLS on February 21, 2023. For more information about the Phase 1 clinical trial for neovascular age-related macular degeneration (nAMD), please visit (). For more information about PMC-403 in SCLS, please visit Dr. Druey's interview on the NIH "I am Intramural" blog (). About PharmAbcine Inc. PharmAbcine is a clinical-stage public company developing next-generation IgG-based therapeutics to treat cancer, neovascular eye diseases, and unmet vascular-related needs. The Company's main pipeline includes clinical assets olinvacimab, PMC-403, and PMC-309. Olinvacimab, the Company's lead asset, is undergoing a Phase II trial in combination with MSD's pembrolizumab for mTNBC patients in Australia to reconfirm the encouraging results from a Phase Ib olinvacimab plus pembrolizumab trial, which delivered 50% ORR, 67% DCR, and a clean safety profile. PMC-403 is a novel TIE2-activating antibody that stabilizes dysfunctional, leaky, and disorganized pathological vessels. It is being tested for neovascular AMD in Phase 1 trials in Korea. PMC-403 is also being explored in other therapeutic areas related to pathological blood vessels, including rare and non-rare vascular-related diseases. PMC-309, a novel anti-VISTA antagonist IgG effective in pan-pH conditions, is an immune checkpoint regulator targeting MDSC (myeloid-derived suppressor cells) and M2 macrophages, which play a pivotal role in maintaining an immunosuppressive tumor microenvironment. A Phase I study is ongoing in Australia, and a Phase Ib/II study combining PMC-309 with pembrolizumab is planned. For additional information about PharmAbcine, visit or follow us on YouTube and LinkedIn. For investor relations and public relations inquiries, please contact: IR/PR Team E-mail: [email protected] SOURCE PharmAbcine 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期孤儿药临床2期临床结果临床申请

2024-07-09

·drugs

Approval for the First Dose Cohort in Phase 1a/b Clinical Trial of PMC-309 in Patients with Advanced or Metastatic Solid Tumors

DAEJEON, South Korea, July 8, 2024. PharmAbcine Inc., a clinical-stage biotech company focusing on next-generation antibody therapeutics, announced that PMC-309, VISTA-targeting immuno-oncology program, received safety approval for the first dose cohort (0.2mg/kg) in Phase 1a/b clinical trial for patients with advanced or metastatic solid tumors in Australia. The second dose cohort (0.5mg/kg) is currently ongoing. The first dose cohort (0.2mg/kg) of PMC-309 was initially administered in January 2024 and received safety approval in April 2024. Currently, the second dose cohort (0.5mg/kg) has been administered to two patients, with the third patient scheduled to receive treatment soon. PMC-309 is an IgG1 monoclonal antibody specifically binding to VISTA on immunosuppressive cells, demonstrating excellent binding affinity at various pH conditions within the tumor microenvironment (TME). By inhibiting VISTA, PMC-309 offers a differentiated mechanism of action, contributing to anti-cancer effects through the activation of T cells, monocytes, and the proliferation of M1 macrophages. This open-label Phase 1a/b clinical trial involves a total of 67 patients and comprises two phases: Phase 1a and Phase 1b. Phase 1a includes PMC-309 monotherapy and combination therapy with KEYTRUDA (pembrolizumab) to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Phase 1b will evaluate the safety and tolerability of PMC-309 monotherapy and combination therapy with KEYTRUDA at the RP2D. The clinical trial is being conducted at four institutions in Australia. Dr. Jin-San Yoo, Chief Executive Officer of PharmAbcine Australia Pty, the Australian subsidiary of PharmAbcine Inc., stated, "It has been 10 years since the first generation of immuno-oncology drugs entered the market. During this time, these drugs have been administered to numerous cancer patients. While some patients have benefited, many have developed resistance, and others have passed away. The need for next-generation immuno-oncology drugs is critical. The confirmation of the safety of the first dose cohort of PMC-309 is just the beginning of this trial. We look forward to gradually verifying the safety and efficacy of PMC-309 through the planned higher dose cohorts. We are also preparing for the combination trial of PMC-309 with KEYTRUDA in collaboration with MSD without any delays." He added, "We are committed to providing new treatment options to patients suffering from the limitations of first-generation immuno-oncology drugs." For more information on the clinical trial, please visit clinicaltrials.gov, identifier NCT05957081. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About PharmAbcine Inc. PharmAbcine is a clinical stage public company developing next generation IgG based therapeutics to treat cancer, neovascular eye diseases, and vascular related unmet needs. The Company's main pipeline include clinical assets olinvacimab, PMC-403, and PMC-309. Olinvacimab, the Company's lead asset, is ongoing a Phase 2 trial in combination with MSD's pembrolizumab for mTNBC patients in Australia to reconfirm the encouraging result from Phase 1b olinvacimab plus pembrolizumab trial, delivering 50% ORR, 67% DCR, and clean safety profile. PMC-403 is a novel TIE2-activating antibody that stabilizes dysfunctional leaky disorganized pathological vessels and can be used for vascular-related eye disease, including wet AMD (Age-related Macular Degeneration). PMC-403 is currently undergoing Phase 1 trial for neovascular AMD patients in Korea. PMC-403 is also being explored to expand into wider therapeutic areas related to pathological vessels including vessel-related rare diseases and non-rare diseases. PMC-309, a novel anti-VISTA-antagonizing IgG in pan pH conditions, is an immune checkpoint regulator that targets MDSC (myeloid derived suppressor cells) and M2 macrophages which play pivotal role in maintaining immunosuppressive TME (Tumor Microenvironment). Phase 1a is ongoing at multicenter in Australia and Phase 1b in combination with MSD's pembrolizumab PMC-309 + Pembrolizumab combo is in plan. PMC-005, is an anti-EGFRviii IgG that only binds to EGFRviii expressed on cancer cells and can be applied to various modalities including CAR-T, CAR-NK, CAR-Macrophage, T cell/NK cell engager, and Radio-Immunotherapy. SOURCE PharmAbcine Keytruda (pembrolizumab) FDA Approval History Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

临床1期临床2期免疫疗法临床申请

2024-07-08

·PRNewswire

PharmAbcine Announces Safety Approval for the First Dose Cohort in Phase 1a/b Clinical Trial of PMC-309 in Patients with Advanced or Metastatic Solid Tumors

PMC-309 receives safety approval for first dose cohort (0.2mg/kg), and second dose cohort (0.5mg/kg) is currently underway in Australia. DAEJEON, South Korea, July 8, 2024 /PRNewswire/ -- PharmAbcine Inc. (KOSDAQ: 208340ks), a clinical-stage biotech company focusing on next-generation antibody therapeutics, announced that PMC-309, VISTA-targeting immuno-oncology program, received safety approval for the first dose cohort (0.2mg/kg) in Phase 1a/b clinical trial for patients with advanced or metastatic solid tumors in Australia. The second dose cohort (0.5mg/kg) is currently ongoing. The first dose cohort (0.2mg/kg) of PMC-309 was initially administered in January 2024 and received safety approval in April 2024. Currently, the second dose cohort (0.5mg/kg) has been administered to two patients, with the third patient scheduled to receive treatment soon. PMC-309 is an IgG1 monoclonal antibody specifically binding to VISTA on immunosuppressive cells, demonstrating excellent binding affinity at various pH conditions within the tumor microenvironment (TME). By inhibiting VISTA, PMC-309 offers a differentiated mechanism of action, contributing to anti-cancer effects through the activation of T cells, monocytes, and the proliferation of M1 macrophages. This open-label Phase 1a/b clinical trial involves a total of 67 patients and comprises two phases: Phase 1a and Phase 1b. Phase 1a includes PMC-309 monotherapy and combination therapy with KEYTRUDA® (pembrolizumab) to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Phase 1b will evaluate the safety and tolerability of PMC-309 monotherapy and combination therapy with KEYTRUDA® at the RP2D. The clinical trial is being conducted at four institutions in Australia. Dr. Jin-San Yoo, Chief Executive Officer of PharmAbcine Australia Pty, the Australian subsidiary of PharmAbcine Inc., stated, "It has been 10 years since the first generation of immuno-oncology drugs entered the market. During this time, these drugs have been administered to numerous cancer patients. While some patients have benefited, many have developed resistance, and others have passed away. The need for next-generation immuno-oncology drugs is critical. The confirmation of the safety of the first dose cohort of PMC-309 is just the beginning of this trial. We look forward to gradually verifying the safety and efficacy of PMC-309 through the planned higher dose cohorts. We are also preparing for the combination trial of PMC-309 with KEYTRUDA® in collaboration with MSD without any delays." He added, "We are committed to providing new treatment options to patients suffering from the limitations of first-generation immuno-oncology drugs." For more information on the clinical trial, please visit clinicaltrials.gov, identifier NCT05957081. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About PharmAbcine Inc. PharmAbcine is a clinical stage public company developing next generation IgG based therapeutics to treat cancer, neovascular eye diseases, and vascular related unmet needs. The Company's main pipeline include clinical assets olinvacimab, PMC-403, and PMC-309. Olinvacimab, the Company's lead asset, is ongoing a Phase 2 trial in combination with MSD's pembrolizumab for mTNBC patients in Australia to reconfirm the encouraging result from Phase 1b olinvacimab plus pembrolizumab trial, delivering 50% ORR, 67% DCR, and clean safety profile. PMC-403 is a novel TIE2-activating antibody that stabilizes dysfunctional leaky disorganized pathological vessels and can be used for vascular-related eye disease, including wet AMD (Age-related Macular Degeneration). PMC-403 is currently undergoing Phase 1 trial for neovascular AMD patients in Korea. PMC-403 is also being explored to expand into wider therapeutic areas related to pathological vessels including vessel-related rare diseases and non-rare diseases. PMC-309, a novel anti-VISTA-antagonizing IgG in pan pH conditions, is an immune checkpoint regulator that targets MDSC (myeloid derived suppressor cells) and M2 macrophages which play pivotal role in maintaining immunosuppressive TME (Tumor Microenvironment). Phase 1a is ongoing at multicenter in Australia and Phase 1b in combination with MSD's pembrolizumab PMC-309 + Pembrolizumab combo is in plan. PMC-005, is an anti-EGFRviii IgG that only binds to EGFRviii expressed on cancer cells and can be applied to various modalities including CAR-T, CAR-NK, CAR-Macrophage, T cell/NK cell engager, and Radio-Immunotherapy. For additional information about PharmAbcine, visit or follow on YouTube and LinkedIn. For licensing deals, joint venture, co-development, and collaboration in research or antibody discovery inquiries, please contact: Business Development Team E-mail: [email protected] Office line: +82 70 4279 5100 For investor relations and public relations inquiries, please contact: IR/PR Team E-mail: [email protected] SOURCE PharmAbcine

免疫疗法临床1期临床2期临床申请

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KEGG	Wiki	ATC	Drug Bank
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适应症	最高研发状态	国家/地区	公司	日期
转移性三阴性乳腺癌	临床2期	澳大利亚	Merck Sharp & Dohme Corp.	2021-09-30
转移性三阴性乳腺癌	临床2期	澳大利亚	PharmAbcine Inc.	2021-09-30
复发性胶质母细胞瘤	临床2期	-	PharmAbcine Inc.	2016-02-04
晚期癌症	临床1期	美国	PharmAbcine Inc.	2011-11-01
肝转移	临床1期	美国	PharmAbcine Inc.	2011-11-01

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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


PS10-18 (SABCS2021)	临床1期	转移性三阴性乳腺癌 PR+ \| HER2-negative	11	Olinvacimab 12mg/kg + Pembrolizumab 200mg	廠壓窪襯衊憲鹹鹽獵製(願廠餘膚遞鏇觸夢蓋鹹) = Haemangiomas were seen in 8 pts accounting for 47 events of CTCAE grade 1 and 21 events of grade 2 製築觸醖襯齋鹹鹹齋齋 (糧衊蓋襯廠壓築構餘艱 ) 更多	积极	2021-02-15
CTNI-14 (SNO2020)	临床2期	复发性胶质母细胞瘤 VEGFR2	15	Olinvacimab 8 mg/kg weekly	網顧膚憲醖繭襯簾蓋廠(淵齋遞網製襯繭遞蓋鹹) = 67% grade 1, 8% grade 2 願衊窪製顧膚製鬱鹹艱 (膚襯鏇夢鏇衊觸餘艱廠 ) 更多	积极	2020-11-09
NCT03722342 (ASCO 12020 \| ASCO 22020) 人工标引	临床1期	复发性胶质母细胞瘤	9	olinvacimab+pembrolizumab	夢繭網鏇蓋製艱鏇選膚(鑰壓繭選願餘遞醖鑰衊) = blurred vision, fatigue, and seizure 鑰蓋顧鑰網鬱繭願鬱窪 (膚製願選範鬱簾鹽獵願 ) 更多	积极	2020-05-29
NCT03033524 (ASCO 12017 \| ASCO 22017) 人工标引	临床2期	复发性胶质母细胞瘤	12	Olinvacimab	醖構製憲顧繭憲襯夢選(鬱鏇憲襯網積簾顧鏇觸) = All SAEs were unrelated to the study drug apart from G2 bleeding haemangioma and G2 cerebral haemorrhage. 艱製鑰鹽範觸膚艱淵築 (願夢網糧廠襯廠夢鹽選 )	积极	2017-06-02
NCT01660360 (ASCO2015)	临床1期	难治恶性实体肿瘤	26	Tanibirumab	鹽製製範淵範齋壓網廠(壓鹽築鹽顧鏇壓艱觸願) = 築鏇夢糧構構餘襯衊夢範夢蓋遞鬱遞襯積窪築 (簾鏇鏇餘蓋壓壓醖鹹艱 ) 更多	-	2015-05-20