A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ascending Doses of G1T48 Alone and in Combination With Palbociclib in Women With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

This is a study to investigate the potential clinical benefit of G1T48 as an oral selective estrogen receptor degrader (SERD) alone and in combination with palbociclib, a cyclin dependent kinase 4/6 (CDK 4/6) inhibitor, in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer.
The study is an open-label design, consisting of 3 parts: dose-finding portion including food effect (Part 1), G1T48 monotherapy expansion portion (Part 2), and G1T48 in combination with palbociclib expansion portion (Part 3). All parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 184 patients may be enrolled in the study.

开始日期2018-05-09

申办/合作机构

G1 Therapeutics, Inc.

100 项与 Rintodestrant 相关的临床结果

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100 项与 Rintodestrant 相关的专利（医药）

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项与 Rintodestrant 相关的文献（医药）

2023-06-01·Clinical cancer research : an official journal of the American Association for Cancer Research

[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant

Communications

作者: Windhorst, Albert D. ; Schuit, Robert C. ; Beelen, Andrew P. ; Boellaard, Ronald ; Yaqub, Maqsood ; de Vries, Elisabeth G.E. ; Menke-van der Houven van Oordt, C. Willemien ; Glaudemans, Andor W.J.M. ; Gebhart, Géraldine ; Iqbal, Ramsha ; Bektas, Huseyyin O. ; Oprea-Lager, Daniela E. ; Aftimos, Philippe

Abstract:

Purpose::

PET with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.

Experimental Design::

In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative, and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS).

Results::

The HS and PFS in the entire group did not correlate (n = 16, Spearman's rho, P = 0.06), but patients with a low HS (< 25.0%, n = 4) had a PFS of > 5 months whereas patients with no [18F]FES uptake (HS 100.0%, n = 3) had a PFS of < 2 months. [18F]FES uptake was not affected by estrogen receptor 1 (ESR1) mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES-positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤ 1–2 half-lives of rintodestrant whereas it restored in patients scanned ≥ 5 days after end of treatment.

Conclusions::

Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs.See related commentary by Linden and Mankoff, p. 2015

2023-04-01·Pharmacological research

SERD-NHC-Au(I) complexes for dual targeting ER and TrxR to induce ICD in breast cancer

Article

作者: Yang, Zhibin ; Liu, Chao ; Liu, Lijuan ; Wen, Zhenfan ; Wang, Xin ; Liang, Zhenlin ; Du, Qianming ; Liu, Wukun ; Lu, Yunlong ; Sheng, Xinyu

The development of selective estrogen receptor degraders (SERDs) has brought new ideas for the clinical treatment of ER-positive advanced breast cancer. The successful application of combinational therapy inspired the exploration of other targets to prevent breast cancer progression. Thioredoxin reductase (TrxR) is an important enzyme that can regulate redox balance in cells and it was considered as a potential target for anticancer treatment. In this study, we firstly combine a clinical SERD candidate--G1T48 (NCT03455270), with a TrxR inhibitor--N-heterocyclic carbene gold(I) [NHC-Au(I)] to form dual targeting complexes that can regulate both signaling pathways. The most efficacious complex 23 exhibited significant antiproliferative profile through degrading ER and inhibiting TrxR activity. Interestingly, it can induce immunogenic cell death (ICD) caused by ROS. This is the first evidence to elucidate the role of ER/TrxR-ROS-ICD axis in ER positive breast cancer and this research may inspire new drug development with novel mechanisms. The in vivo xenograft study demonstrated that complex 23 had excellent antiproliferative activity toward MCF-7 cells in mice model.

2022-06-03·Expert opinion on investigational drugs2区 · 医学

Latest generation estrogen receptor degraders for the treatment of hormone receptor-positive breast cancer

2区 · 医学

Review

作者: Yu, Jiajie ; Metcalfe, Ciara ; Perez-Moreno, Pablo D. ; Chen, Ya-Chi ; Wang, Xiaojing ; Malhi, Vikram ; De Bruyn, Tom ; Gelzleichter, Thomas

INTRODUCTION:

The selective estrogen receptor degrader (SERD) and full receptor antagonist provides an important therapeutic option for hormone receptor (HR)-positive breast cancer. Endocrine therapies include tamoxifen, a selective estrogen receptor modulator (SERM), that exhibits receptor agonist and antagonist activity, and aromatase inhibitors that block estrogen biosynthesis but which demonstrate acquired resistance. Fulvestrant, the only currently approved SERD, is limited by poor drug-like properties. A key focus for improving disease management has been development of oral SERDs with optimized target occupancy and potency and superior clinical efficacy.

AREAS COVERED:

Using PubMed, clinicaltrials.gov, and congress websites, this review explored the preclinical development and clinical pharmacokinetics from early phase clinical studies (2015 or later) of novel oral SERDs, including giredestrant, amcenestrant, camizestrant, elacestrant, and rintodestrant.

EXPERT OPINION:

Numerous oral SERDs are in clinical development, aiming to form the core endocrine therapy for HR-positive breast cancer. Through property- and structure-based drug design of estrogen receptor-binding, antagonism, degradation, anti-proliferation, and pharmacokinetic properties, these SERDs have distinct profiles which impact clinical dosing, efficacy, and safety. Assuming preliminary safety and activity data are confirmed in phase 3 trials, these promising agents could further improve the management, outcomes, and quality of life in HR-positive breast cancer.

项与 Rintodestrant 相关的新闻（医药）

2022-06-07

·PRNewswire

SERD Therapeutics Market worth $ 5.75 Billion by 2030 - Exclusive Report by InsightAce Analytic

JERSEY CITY, N.J., June 7, 2022 /PRNewswire/ -- InsightAce Analytic Pvt. Ltd. announces the release of market assessment report on "Global SERD Therapeutics Market (Products (Faslodex, RAD1901, GDC-9545, AZD9833, SAR439859, and Other Generics), Therapy (First-Line Treatment, Second-Line Treatment))– Industry Analysis, Competitive Landscape, Revenue Forecast 2020-2030" According to the latest research by InsightAce Analytic, the global SERD therapeutics market size valued at US$ 1.33 billion, and it is expected to reach US$ 5.75 billion in 2030, recording a promising CAGR of 17.9% during the period of 2020-2030. Selective estrogen receptor degrader (SERD) is a type of drug which downregulates the estrogen receptor. SERD and full receptor antagonist are essential treatment options for HR-positive breast cancer. Tamoxifen, a particular estrogen receptor modulator (SERM) with receptor agonist and antagonist action, and aromatase inhibitors, which prevent estrogen production, but cause acquired resistance, are examples of endocrine medicines. Fulvestrant, the only SERD currently licensed, has weak drug-like characteristics. The development of oral SERDs with optimal target occupancy and potency and enhanced clinical performance has been a primary emphasis for improving disease management. The increasing investments by key players in the development of promising breast cancer therapies are anticipated to fuel the SERD therapeutics market growth over the forecast period. Request for Sample Pages: Major driving factors in the SERD therapeutics market are the increasing need for SERD therapies, the high prevalence of breast cancer, rising number of clinical trials. Furthermore, the fast adoption of advanced medical technologies, population growth, and a growing number of health-conscious people will enhance the growth of the SERD therapeutics market. However, the high price of devices, complex procedures, and resistance to endocrine therapy is restraining the development of this market. Moreover, the COVID-19 pandemic has both positively and negatively impacted the SERD therapeutics market due to the lockdown situations. At the regional level, the North American region is the major revenue holder of this market due to rising awareness about SERD therapies, increasing government investments in the research and development of therapies for the treatment of various cancer diseases, and the rising prevalence of breast cancer. On the other hand, the Europe region will also dominate the market during the forecast period due to the advancements in the biopharmaceutical field, stringent regulations, and the increasing prevalence of chronic diseases. The Asia-Pacific market is projected to show significant growth in the future due to the growing SERD therapeutic industries and fast adaption of new technologies. Enquiry Before Buy: Leading manufacturers in this field are focusing on novel SERD therapy innovations, making new partnerships, collaborations and agreements, growing awareness about SERD therapies, and increasing research investments for developing advanced technologies. These strategies will propel their growth opportunities in the market. In 2020, QLHC announced an evaluation of Sanofi's SAR439859, an oral estrogen receptor degrader (SERD), in a new I-SPY 2 study arm targeting patients with newly diagnosed hormone receptor-positive (HR+) clinical stage 2/3 invasive breast cancer. AstraZeneca moved its next-generation oral SERD AZD9833 into phase 1 in 2018. While work on AZD9496 stalled after a few early clinical trials, AstraZeneca has quickly expanded and advanced the development of AZD9833. Late last month, AstraZeneca began enrolling patients in the phase 3 clinical trial of AZD9833. Major key Players in the SERD therapeutics market are Amneal Pharmaceuticals Inc, AstraZeneca, Plc., Dr Reddy's Laboratories, Eli Lilly and Company, G1 Therapeutics, Inc., Glenmark Pharmaceuticals, HBT Labs, Inc, Hoffmann-La Roche AG, InventisBio, Novartis AG, Radius Health, Sanofi S.A., Teva Pharmaceutical Industries Ltd., Zenopharm LLC., Zentalis Pharmaceuticals, and List of Other Prominent Players. Recent Key Developments: In June 2021, Eli Lilly and Company presented new results for the exploratory use of Verzenio® (abemaciclib) in high-risk early breast cancer, as well as for its oral selective oestrogen receptor degrader (SERD) LY3484356 (ASCO). Lilly is releasing an exploratory analysis from the positive Phase 3 monarch study testing Verzenio, a CDK4/6 inhibitor, in a subset of patients with HR+, HER2-, high-risk early breast cancer (EBC) who had had neoadjuvant chemotherapy. In Sept 2020, InventisBio recently announced the conclusion of a $147 million series D fundraising, which included several of the world's leading biopharmaceutical and healthcare venture capital firms. InventisBio currently has three medicinal compounds in various stages of clinical development, and one new product has recently begun a worldwide phase I clinical trial. D-0502 showed remarkable anti-tumour effectiveness in phase 1 research, with superior absorption and an acceptable safety profile when compared to other oral SERDs in clinical development throughout the world. In Sept 2019, Preliminary data from a Phase 1/2a dose-escalation trial of G1T48, an oral selective oestrogen receptor degrader (SERD), in patients with oestrogen receptor-positive, HER2-negative (ER+, HER2-) breast cancer were released by G1 Therapeutics, Inc. G1T48 was well tolerated in the study and showed anti-tumour effectiveness in patients who had been substantially pre-treated. The results of this trial support the future development of G1T48 in both first line and adjuvant settings, and a first-line Phase 3 pivotal trial is expected to begin in 2020. Market Segments Market Size (Value US$ Mn) & Forecasts and Trend Analyses, 2020 to 2030 based on Products Faslodex RAD1901 GDC-9545 AZD9833 SAR439859 Other Generics Market Size (Value US$ Mn) & Forecasts and Trend Analyses, 2020 to 2030 based on Therapy First-Line Treatment Second-Line Treatment Market Size (Value US$ Mn) & Forecasts and Trend Analyses, 2020 to 2030 based on Region North America Europe Asia Pacific Latin America Middle East & Africa North America SERD therapeutics market revenue (US$ Million) by Country, 2020 to 2030 U.S. Canada Europe SERD therapeutics market revenue (US$ Million) by Country, 2020 to 2030 Germany France Italy Spain Russia Rest of Europe Asia Pacific SERD therapeutics market revenue (US$ Million) by Country, 2020 to 2030 India China Japan South Korea Australia & New Zealand Latin America SERD therapeutics market revenue (US$ Million) by Country, 2020 to 2030 Brazil Mexico Rest of Latin America Middle East & Africa SERD therapeutics market revenue (US$ Million) by Country, 2020 to 2030 GCC Countries South Africa Rest of Middle East & Africa Why should buy this report: To receive a comprehensive analysis of the prospects for global SERD therapeutics market To receive industry overview and future trends of global SERD therapeutics market To analyse the SERD therapeutics market drivers and challenges To get information on SERD therapeutics market size value (US$ Mn) forecast till 2030 Major Investments, Mergers & Acquisition in global SERD therapeutics market industry For Customization @ Other Related Reports Published by InsightAce Analytic: Global RNA-based Therapeutics Market Global Stem Cell Exosome Therapeutic Market Global Antisense Oligonucleotide Therapeutics Market Global Oncolytic Virus Therapy Market Global Immuno-Oncology Cell Therapy Market About Us: InsightAce Analytic is a market research and consulting firm that enables clients to make strategic decisions. Our qualitative and quantitative market intelligence solutions inform the need for market and competitive intelligence to expand businesses. We help clients gain competitive advantage by identifying untapped markets, exploring new and competing technologies, segmenting potential markets and repositioning products. Our expertise is in providing syndicated and custom market intelligence reports with an in-depth analysis with key market insights in a timely and cost-effective manner. Contact Us: InsightAce Analytic Pvt. Ltd. Tel.: +1 718 593 4405 Email: [email protected] Site Visit: Follow Us on LinkedIn @ bit.ly/2tBXsgS Follow Us On Facebook @ bit.ly/2H9jnDZ SOURCE InsightAce Analytic Pvt. Ltd.

仿制药寡核苷酸细胞疗法并购合作

2021-06-04

·GlobeNewswire

G1 Therapeutics Presents Phase 1 Data at ASCO Describing

- Combination of Rintodestrant and Palbociclib was Very Well Tolerated with No Reported Discontinuations due to Treatment-Emergent Adverse Events (TEAEs) - - 60% Clinical Benefit Rate Achieved in Full Analysis Set at Week 24 - RESEARCH TRIANGLE PARK, N.C., June 04, 2021 (GLOBE NEWSWIRE) -- G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, today presented results from its Phase 1 study of its oral selective estrogen receptor degrader (SERD), rintodestrant, demonstrating the drug was very well tolerated and did not result in additional or more severe toxicities when added to palbociclib for the treatment of ER+/HER2- advanced breast cancer. In addition, encouraging antitumor activity was observed in the study, with a doubling of the clinical benefit rate (defined by percentage of patients with either confirmed complete or partial response or stable disease lasting ≥ 24 weeks) from 30 percent with rintodestrant monotherapy to 60 percent with the combination of rintodestrant and palbociclib. This effect included patients with tumors harboring ESR1 variants, which are known to modulate breast cancer severity and resistance to hormone therapy. These data are being presented at the American Society of Clinical Oncology (ASCO) annual virtual meeting, and the posters are available in the scientific publications section of G1’s website. “Between 30% and 50% of estrogen-positive tumors become resistant to selective estrogen receptor modulators (SERMs), so it is imperative that new and well tolerated approaches to overcoming resistance and improving response rates are developed,” said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. “We previously demonstrated that rintodestrant monotherapy has a favorable safety profile in patients with heavily pretreated ER+/HER2- advanced breast cancer, and the third arm now shows that the combination of rintodestrant and palbociclib provides the same favorable safety profile as well as important indicators of antitumor activity warranting further evaluation of the potential of this combination. Importantly, no ocular toxicity or bradycardia was observed during this trial, both of which are common adverse events observed in trials of other oral SERDs. These data add to the potential for rintodestrant to be an active and well-tolerated oral SERD for the treatment of ER+, HER2- breast cancer as we ultimately seek to out-license the drug." The Phase 1, first-in-human, open-label study evaluated rintodestrant in women with ER+/HER2- advanced breast cancer after progression on endocrine therapy. The study comprised three parts: dose escalation of monotherapy rintodestrant (part 1), dose expansion of monotherapy rintodestrant (part 2), and rintodestrant in combination with palbociclib therapy (part 3). The results of part 1 and 2 were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS) (2020 poster). Forty participants in the third part of the study received 800 mg of continuous rintodestrant once daily combined with 125 mg of palbociclib once daily for 21 days in 28-day cycles. This patient population had received a high degree of prior chemotherapy in the advanced setting (48%) and had visceral disease (68%); these tend to be patients that respond less well to CDK4/6 inhibitors in combination with endocrine therapies (ETs). The primary objective was safety and tolerability of rintodestrant with palbociclib, and the secondary objective was antitumor activity, including best overall response, progression-free survival (PFS), overall survival and clinical benefit rate, among other parameters. Key study findings with a median duration of treatment of 6.2 months in the ongoing Phase 1 combination trial presented in the poster include: Safety: Antitumor Activity: The Company is in the process of evaluating partnering options for rintodestrant. About G1 TherapeuticsG1 Therapeutics, Inc. is a commercial-stage biopharmaceutical company focused on the development and commercialization of next generation therapies that improve the lives of those affected by cancer, including the Company’s first commercial product, COSELA™ (trilaciclib). G1 has a deep clinical pipeline and is executing a tumor-agnostic development plan evaluating COSELA in a variety of solid tumors, including colorectal, breast, lung, and bladder cancers. G1 Therapeutics is based in Research Triangle Park, N.C. For additional information, please visit and follow us on Twitter @G1Therapeutics. G1 Therapeutics™ and the G1 Therapeutics logo are trademarks of G1 Therapeutics, Inc. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this press release include, but are not limited to, those relating to expectations for the therapeutic potential of rintodestrant, and the possibility to realize the economic impact in the US market presented in the scientific analyses described above, and rintodestrant may fail to achieve the degree of market acceptance for commercial success, are based on the company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause the company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in the company’s filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein and include, but are not limited to, the company’s ability to complete a successful commercial launch for COSELA (trilaciclib); the company’s ability to complete clinical trials for, obtain approvals for and commercialize any of its product candidates other than COSELA (trilaciclib); the company’s initial success in ongoing clinical trials may not be indicative of results obtained when these trials are completed or in later stage trials; the inherent uncertainties associated with developing new products or technologies and operating as a commercial-stage company; and market conditions. Except as required by law, the company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. G1 Therapeutics Contact:Will RobertsVice President, Investor Relations & Corporate Communications919-907-1944wroberts@g1therapeutics.com

小分子药物ASCO会议

2021-05-19

·GlobeNewswire

G1 Therapeutics Announces Upcoming Data at the American

RESEARCH TRIANGLE PARK, N.C., May 19, 2021 (GLOBE NEWSWIRE) -- G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, today announced upcoming data presentations at the American Society of Clinical Oncology (ASCO) annual meeting, being held virtually June 4th through 8th. The presentations will describe results from the Company’s study of its oral selective estrogen receptor degrader (SERD), rintodestrant, in combination with palbociclib for the treatment of ER+/HER2- advanced breast cancer as well as data describing the effects of COSELA™ (trilaciclib) on T-cell activation and clonal expansion in patients with newly diagnosed extensive-stage small cell lung cancer. A copy of the posters will be made available on the G1 corporate website on June 4, 2021. Details for the posters and abstract are as follows: Title: Rintodestrant (G1T48), an oral selective estrogen receptor degrader, in combination with palbociclib for ER+/HER2- advanced breast cancer: Phase 1 results. Session: Breast Cancer – MetastaticDate: Available starting on June 04, 2021, 09:00 AM ETPoster number: 1063 Title: Effects of trilaciclib prior to chemotherapy ± atezolizumab on T-cell activation in patients with newly diagnosed extensive-stage small cell lung cancer.Session: Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic CancersDate: Available starting on: May 19, 2021, 05:00 PM ETeAbstract: e20582 Title: PRESERVE 2: A phase 3, randomized, double-blind trial of trilaciclib versus placebo in patients receiving first- or second-line gemcitabine and carboplatin for locally advanced unresectable or metastatic triple-negative breast cancer. Session: Breast Cancer – MetastaticDate: Available starting on June 04, 2021, 09:00 AM ETPoster number: TPS1107 About G1 TherapeuticsG1 Therapeutics, Inc. is a commercial-stage biopharmaceutical company focused on the development and commercialization of next generation therapies that improve the lives of those affected by cancer, including the Company’s first commercial product, COSELA™ (trilaciclib). G1 has a deep clinical pipeline and is executing a tumor-agnostic development plan evaluating COSELA in a variety of solid tumors, including colorectal, breast, lung, and bladder cancers. G1 Therapeutics is based in Research Triangle Park, N.C. For additional information, please visit and follow us on Twitter @G1Therapeutics. G1 Therapeutics™ and the G1 Therapeutics logo and COSELA™ and the COSELA logo are trademarks of G1 Therapeutics, Inc. G1 Therapeutics Contact:Will RobertsVice President, Investor Relations & Corporate Communications919-907-1944wroberts@g1therapeutics.com

小分子药物ASCO会议

100 项与 Rintodestrant 相关的药物交易

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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
乳腺癌	临床2期	摩尔多瓦	G1 Therapeutics, Inc.	2020-12-08
晚期乳腺癌	临床1期	美国	G1 Therapeutics, Inc.	2018-05-09
晚期乳腺癌	临床1期	比利时	G1 Therapeutics, Inc.	2018-05-09
晚期乳腺癌	临床1期	保加利亚	G1 Therapeutics, Inc.	2018-05-09
晚期乳腺癌	临床1期	格鲁吉亚	G1 Therapeutics, Inc.	2018-05-09
晚期乳腺癌	临床1期	摩尔多瓦	G1 Therapeutics, Inc.	2018-05-09
晚期乳腺癌	临床1期	荷兰	G1 Therapeutics, Inc.	2018-05-09
晚期乳腺癌	临床1期	乌克兰	G1 Therapeutics, Inc.	2018-05-09
乳腺导管癌	临床1期	美国	G1 Therapeutics, Inc.	2018-05-09
乳腺导管癌	临床1期	比利时	G1 Therapeutics, Inc.	2018-05-09

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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


NCT03455270 (ASCO2021) 人工标引	临床1期	晚期乳腺癌 ER Positive \| HER2 Negative	40	palbociclib+Rintodestrant	醖醖築顧淵醖廠艱糧齋(鏇艱膚憲觸夢艱糧製鑰) = neutropenia was 38%/15% 憲範齋鹹觸醖繭膚顧鏇 (構艱鏇繭遞觸獵夢鬱範 ) 更多	积极	2021-05-28