更新于：2024-12-05
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重组人源化抗HER2单抗-AS269偶联物(Ambrx)
更新于：2024-12-05
概要
基本信息
原研机构 |
非在研机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)临床3期 |
特殊审评快速通道 (美国)、突破性疗法 (中国)、孤儿药 (美国) |
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序列信息
Sequence Code 18481L
来源: *****
Sequence Code 622617079H
来源: *****
关联
19
项与 重组人源化抗HER2单抗-AS269偶联物(Ambrx) 相关的临床试验Phase II Open-label Study of ARX788 (Anti-HER2 Antibody Drug Conjugate) for Patients With HER2-low Locally Advanced Unresectable / Metastatic Breast Cancer
Evaluate the Efficacy and Safety of ARX788 Given Every 6 Weeks in Patients with HER2-positive Advanced Breast Cancer
Evaluate the Efficacy and Safety of ARX788 in Patients With HER2-positive Advanced Breast Cancer Whose Disease Has Progressed Following T-DXd Therapy
100 项与 重组人源化抗HER2单抗-AS269偶联物(Ambrx) 相关的临床结果
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100 项与 重组人源化抗HER2单抗-AS269偶联物(Ambrx) 相关的转化医学
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100 项与 重组人源化抗HER2单抗-AS269偶联物(Ambrx) 相关的专利（医药）
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13
项与 重组人源化抗HER2单抗-AS269偶联物(Ambrx) 相关的文献（医药）2023-08-31JNCI cancer spectrum
Toxicity profiles of antibody-drug conjugates for anticancer treatment: a systematic review and meta-analysis.
Review
作者: Suzuki, Yukio ; Ota, Yukihide ; Takagi, Hisato ; Harrington, Matthew ; Kuno, Toshiki ; Wright, Jason D ; Miyagi, Etsuko ; Zhou, Susu
BACKGROUND:
Antibody-drug conjugates are attractive targeted agents in anticancer treatment because of their unique mechanism of action and reduced toxicity. Little is known about the spectrum of adverse events associated with antibody-drug conjugates, despite tens of clinical trials.
METHODS:
A systematic review of randomized controlled trials evaluating antibody-drug conjugate efficacy in anticancer treatment was conducted. PubMed, EMBASE, and ClinicalTrial.gov were searched for relevant studies. Meta-analyses assessed the odds ratios (ORs) of 12 treatment-related symptoms and toxicities in patients treated with antibody-drug conjugates compared with those receiving other anticancer agents without antibody-drug conjugates. All-grade and high-grade (grade ≥3) toxicities were examined.
RESULTS:
Twenty studies involving 10 075 patients were included. Compared with control groups, antibody-drug conjugates were associated with a higher risk of all-grade fatigue (OR = 1.25, 95% confidence interval [CI] = 1.08 to 1.45), anorexia (OR = 1.36, 95% CI = 1.09 to 1.69), nausea (OR = 1.46, 95% CI = 1.09 to 1.97), and sensory neuropathy (OR = 2.18, 95% CI = 1.27 to 3.76) as treatment-related symptoms. Patients treated with antibody-drug conjugates had a statistically significantly lower risk of all-grade febrile neutropenia (OR = 0.46, 95% CI = 0.22 to 0.96). Conversely, they had a higher risk of thrombocytopenia (OR = 2.07, 95% CI = 1.00 to 4.31), increased alanine aminotransferase (OR = 2.51, 95% CI = 1.84 to 3.40), and increased aspartate aminotransferase (OR = 2.83, 95% CI = 2.04 to 3.93). Subgroup analysis showed a similar toxicity profile when comparing the solid tumors with hematologic malignancy groups and the antibody-drug conjugate vs antibody-drug conjugate plus chemotherapy groups, except for some neurologic and hematologic adverse events.
CONCLUSIONS:
This comprehensive profile of adverse events associated with antibody-drug conjugate-based treatment shows an increase in various types of all-grade treatment-related symptoms and adverse events, although no increase in high-grade adverse events was seen.
2022-11-01Cell reports. Medicine
Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma
Article
作者: Liang, Xue-Jun ; Xiong, Gao-Zhun ; Zhang, Yang ; Xia, Gang ; Yuan, Xiang-Lin ; Shen, Ao ; Ji, Yan-Ping ; Qiu, Miao-Zhen ; Zhao, Qi ; Xu, Rui-Hua ; Zhang, Yan-Qiao ; Wang, De-Shen ; Zhang, Tao ; Zhao, Hong-Yun ; Wei, Xiao-Li ; Wang, Ju-Feng
ARX788 is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate with AS269 as cytotoxic payload. In this phase 1 multicenter dose-expansion clinical trial, patients with HER2-positive advanced gastric/gastroesophageal junction adenocarcinoma failing to respond to prior trastuzumab-based standard treatment were enrolled. Between July 15th, 2019, and March 14th, 2022, 30 participants were enrolled. Twenty-eight (93.3%) patients experienced at least one drug-related adverse event (AE) and 13.3% experienced grade 3 ARX788-related AEs. The confirmed objective response rate is 37.9% (95% confidence interval [CI]: 20.7%-57.7%) and the disease control rate is 55.2% (95% CI: 35.7%-73.6%). With a median follow up of 10 months, the median progression-free survival and overall survival are 4.1 (95% CI: 1.4-6.4) and 10.7 months (95% CI: 4.8-not reached), respectively. The median duration of response is 8.4 (95% CI: 2.1-18.9) months. ARX788 is well tolerated and has promising anti-tumor activity in patients with HER2-positive advanced gastric adenocarcinoma (ChinaDrugTrials.org.cn: CTR20190639).
2022-10-03Clinical cancer research : an official journal of the American Association for Cancer Research
Phase I Trial of a Novel Anti-HER2 Antibody–Drug Conjugate, ARX788, for the Treatment of HER2-Positive Metastatic Breast Cancer
Article
作者: Ji, Dongmei ; Shen, Weina ; Xiao, Qin ; Gu, Yajia ; Hu, Xichun ; O'Shaughnessy, Joyce ; Zhang, Jian
Abstract:
Purpose::
ARX788 is a novel antibody–drug conjugate (ADC) comprised of an anti-HER2 mAb and a potent tubulin inhibitor payload AS269 that is site-specifically conjugated to the antibody via a nonnatural amino acid incorporated into the antibody. Herein, we present the results of a phase I study of the safety, pharmacokinetics, and antitumor activity of ARX788 in patients with HER2-positive metastatic breast cancer (MBC).
Patients and Methods::
Patients with HER2-positive MBC received ARX788 at doses of 0.33, 0.66, 0.88, 1.1, 1.3, or 1.5 mg/kg every 3 weeks, or 0.88, 1.1, or 1.3 mg/kg every 4 weeks. The dose-limiting toxicity (DLT) was assessed for 84 days for pulmonary toxicity and at a duration of one cycle (21 or 28 days) for other toxicities.
Results::
In total, 69 patients were enrolled. No DLT or drug-related deaths occurred. Most patients (67/69; 97.1%) experienced at least one treatment-related adverse event (TRAE). Common (≥ 30%) TRAEs included an increase in aspartate aminotransferase, an increase in alanine aminotransferase, corneal epitheliopathy, alopecia, hypokalemia, interstitial lung disease (ILD)/pneumonitis, and an increase in aldosterone. While 34.8% of participants experienced ILD/pneumonitis, only 2 had a severity of grade 3. At 1.5 mg/kg every 3 weeks, the recommended phase II dose, the objective response rate was 65.5% [19/29, 95% confidence interval (CI), 45.7–82.1], the disease control rate was 100% (95% CI, 81.2–100), and the median progression-free survival was 17.02 months (95% CI, 10.09–not reached).
Conclusions::
ARX788 demonstrated a manageable safety profile with promising preliminary signs of activity in patients with HER2-positive MBC who progressed on prior anti-HER2 therapies.
研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| HER2阳性胃癌 | 临床3期 | 中国 | 2021-08-02 | |
| HER2阳性乳腺癌 | 临床3期 | 中国 | 2020-08-19 | |
| 胃癌 | 临床3期 | - | - | |
| HER2低表达乳腺癌 | 临床2期 | 美国 | 2025-01-31 | |
| HR阳性乳腺腺癌 | 临床2期 | 美国 | 2025-01-31 | |
| HR阳性乳腺癌 | 临床2期 | 美国 | 2025-01-31 | |
| 三阴性乳腺癌 | 临床2期 | 美国 | 2025-01-31 | |
| 胆道癌 | 临床2期 | 美国 | 2021-11-05 | |
| 结直肠癌 | 临床2期 | 美国 | 2021-11-05 | |
| HER2突变型非小细胞肺癌 | 临床2期 | 美国 | 2021-11-05 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2/3期 | HER2阳性乳腺癌 HER2+ | - | (製範製簾築艱鬱鹽顧願) = 壓艱繭選廠醖鹽鬱製鬱 鹹鹽醖網顧積鑰齋襯鏇 (膚夢窪簾鏇網鑰醖襯顧 ) | 积极 | 2024-05-24 | ||
(製範製簾築艱鬱鹽顧願) = 鏇構範齋選範構膚齋範 鹹鹽醖網顧積鑰齋襯鏇 (膚夢窪簾鏇網鑰醖襯顧 ) | |||||||
临床1期 | 12 | ARX788 1.3mg/kg + Toripalimab 240mg | 願築廠鹹製壓獵鹹選遞(簾廠鑰願膚蓋願積夢構) = 蓋鏇獵網糧憲遞鬱艱顧 顧簾鹽齋餘衊觸憲繭醖 (壓糧願顧鹽製醖鏇鹽願 ) 更多 | 积极 | 2024-05-24 | ||
ARX788 1.5mg/kg + Toripalimab 240mg | 願築廠鹹製壓獵鹹選遞(簾廠鑰願膚蓋願積夢構) = 願積膚積鏇鹽簾衊襯網 顧簾鹽齋餘衊觸憲繭醖 (壓糧願顧鹽製醖鏇鹽願 ) 更多 | ||||||
临床3期 | HER2阳性转移性乳腺癌 HER2 Positive | 441 | 顧衊構餘顧積選夢選齋(範積築夢壓淵築製選餘) = The pivotal Phase 3 ACE-Breast-02 study met its pre-specified interim primary efficacy endpoint with statistical significance, demonstrating a greater progression free survival benefit compared to the control 艱積鹹齋鏇窪壓選襯選 (蓋觸選選窪醖觸製鏇醖 ) 达到 | 积极 | 2023-01-03 | ||
临床2期 | HER2阳性转移性乳腺癌 HER2 Positive | 7 | 遞鏇糧遞選齋顧網簾鏇(醖膚觸築壓構製窪鹹醖) = 鏇餘願築鑰繭艱艱襯夢 淵製憲淵膚窪廠鑰築築 (糧齋繭積築獵廠艱選觸 ) 更多 | 积极 | 2022-12-09 | ||
临床1期 | 30 | 網蓋憲製艱壓鑰網廠醖(鑰顧遞餘糧艱願網醖觸) = 廠製鬱醖範艱齋鬱淵製 醖齋鹽遞獵簾選簾襯膚 (夢壓齋積襯鹽繭積醖憲 ) 更多 | 积极 | 2022-11-15 | |||
临床1期 | HER2阳性转移性乳腺癌 HER2 Positive | 69 | 鹹繭鬱繭築獵遞遞鏇壓(襯繭網艱網艱鏇製築餘) = 願鑰鏇鏇膚鬱鬱鹹齋鹹 餘膚獵製簾繭構餘壓製 (積艱鑰網醖襯淵簾窪憲, 10.09 ~ NR) 更多 | 积极 | 2022-05-26 | ||
临床1期 | 30 | 壓廠醖襯淵鑰衊鏇網製(襯膚糧憲築顧網範醖觸) = 3级 鏇醖襯憲顧廠壓醖選鬱 (餘餘選艱淵壓齋顧繭廠 ) 更多 | - | 2021-09-25 | |||
临床1期 | 实体瘤 HER2 Overexpression | 34 | 鹽糧廠膚齋窪鏇鏇膚製(鑰鹹獵簾簾網夢鬱鏇廠) = pneumonitis (2.9%) and fatigue (2.9%) 築壓糧廠衊鏇憲蓋簾製 (網鏇齋糧憲築衊齋觸獵 ) 更多 | 积极 | 2021-05-28 | ||
临床1期 | 23 | 窪網廠艱觸壓獵糧網觸(遞願範窪衊築壓網艱繭) = Most AEs were grade 1 or 2 and were manageable. There were 2 drug-related grade 3 AEs and no grade 4 or 5 AEs occurred. 鑰齋製網範鬱鏇願壓鹽 (獵遞鑰夢夢膚遞衊膚範 ) | 积极 | 2021-05-28 | |||
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