A Single-Arm, Open-Label Phase Ia/Ib Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of FS-207 in Patients With Advanced Solid Tumors With High Microsatellite Instability (MSI-H)
This is a Phase Ia/Ib clinical study of FS-207, an investigational oral tablet, in patients with advanced solid tumors that are microsatellite instability-high, also called MSI-H. MSI-H tumors have specific changes in DNA repair pathways and may depend on the WRN protein to survive. FS-207 is designed to inhibit WRN.
The main purpose of this study is to evaluate the safety and tolerability of FS-207 and to understand how the drug moves through the body. The study will also look for early signs of anti-tumor activity.
This study has two parts. In the first part, called dose escalation, small groups of patients will receive increasing dose levels of FS-207 to help identify a safe and appropriate dose for further study. In the second part, called dose expansion, additional patients with selected MSI-H advanced solid tumors will receive FS-207 at dose level(s) chosen based on the earlier safety and clinical data.
Participants will take FS-207 orally once daily. Study doctors will monitor participants closely through physical examinations, blood and urine tests, electrocardiograms, heart function tests, imaging scans, and blood samples for pharmacokinetic testing. Tumor assessments will be performed regularly to evaluate whether the cancer has responded to treatment, remained stable, or progressed.
This is an open-label study, which means that both the participants and study doctors will know that FS-207 is being given. There is no placebo group in this study.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Linsen Li, Ph.D.
- 電話番号：86-18761061234
- メール：lilinsen@foresightbiopharm.com
研究場所
-
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Beijing、中国、100730
- Peking Union Medical College Hospital
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Beijing、中国、100142
- Peking University Cancer Hospital
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コンタクト：
- Lin Shen, M.D.
- 電話番号：86-010-88196561
- メール：doctorshenlin@sina.cn
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Shanghai、中国、200072
- Shanghai Tenth People's Hospital
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Anhui
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Hefei、Anhui、中国
- The First Affiliated Hospital of Anhui Medical University
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Fujian
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Fuzhou、Fujian、中国、350014
- Fujian Cancer Hospital
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Guangdong
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Guangzhou、Guangdong、中国、510080
- Guangdong Provincial People's Hospital
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Henan
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Zhengzhou、Henan、中国、450052
- The First Affiliated Hospital of Zhengzhou University
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Hubei
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Wuhan、Hubei、中国、430030
- Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
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Hunan
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Changsha、Hunan、中国、410013
- Hunan Cancer Hospital
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Jiangxi
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Nanchang、Jiangxi、中国、330029
- Jiangxi Cancer Hospital
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Jilin
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Changchun、Jilin、中国、130012
- Jilin cancer hospital
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Liaoning
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Shenyang、Liaoning、中国、110001
- The First Affiliated Hospital of China Medical University
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Ningxia
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Yinchuan、Ningxia、中国、750004
- General Hospital of Ningxia Medical University
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Shandong
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Jinan、Shandong、中国、250117
- Cancer Hospital of Shandong First Medical School
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Qingdao、Shandong、中国、266000
- The Affiliated Hospital of Qingdao University
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Sichuan
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Chengdu、Sichuan、中国、610041
- West China Hospital,Sichuan University
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Zhejiang
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Hangzhou、Zhejiang、中国、310009
- The Second Affiliated Hospital Zhejiang University School of Medicine
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 1) Male or female patients aged ≥18 years at the time of signing the Informed Consent Form; 2) Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors, whose disease has progressed or who have experienced intolerable toxicity following prior standard therapy. Additionally, participants must meet the following criterion: they have previously received treatment with at least one immune checkpoint inhibitor (ICI), and this treatment was deemed a failure due to disease progression or was discontinued due to intolerable toxicity; 3) Participants must provide a test report confirming a positive MSI-H/dMMR status in their tumor tissue; 4) Eastern Cooperative Oncology Group (ECOG) Performance Status score: 0-1; 5) Anticipated life expectancy of ≥3 months; 6) Presence of at least one measurable lesion (according to RECIST v1.1 criteria, a measurable lesion is defined as a non-lymph node lesion with a longest diameter of ≥10 mm, or a lymph node lesion with a short axis of ≥15 mm, as measured by CT or MRI); 7) Female or male participants of childbearing potential must agree not to conceive, donate ova, or donate sperm from the date of signing the Informed Consent Form until 3 months after the last treatment administered in the study; furthermore, during this period, they must agree to utilize effective contraception (including one or more non-pharmacological contraceptive methods) or safety measures; 9) Agrees to comply with all requirements and procedures of the clinical trial and voluntarily signs the Informed Consent Form.
Exclusion Criteria:
1) Known diagnosis of Werner syndrome; 2) Prior treatment with any medication targeting Werner syndrome helicase (WRN); 3) Receipt of any anti-tumor therapy within 3 weeks or 5 half-lives (whichever is longer) prior to the first dose; 4) Patients with adverse events related to prior anti-tumor therapy that have not resolved to Grade ≤1 (according to NCI CTCAE v6.0), excluding toxicities deemed by the investigator to pose no safety risk-such as alopecia, Grade 2 peripheral neuropathy, hypothyroidism stable on hormone replacement therapy, mild rash, hyperpigmentation, etc.-with specific cases subject to the investigator's judgment; 5) Undergone, or scheduled to undergo during the study period, major surgery (excluding procedures for vascular access placement, or biopsies performed via laparoscopy, mediastinoscopy, or thoracoscopy) within 4 weeks prior to the first dose; or undergone radical radiotherapy (palliative radiotherapy within 2 weeks prior to the first dose); 6) Leptomeningeal metastases; central nervous system (CNS) metastases with clinical symptoms; or other evidence indicating that CNS metastases are not adequately controlled, as determined by the investigator to render the participant unsuitable for enrollment. 7) Patients with symptomatic and unstable pleural effusion, ascites, or pericardial effusion, as determined by the investigator (patients whose clinical symptoms stabilize following therapeutic drainage of pleural fluid, ascites, or pericardial fluid may be enrolled); 8) Patients with other severe or uncontrolled systemic diseases, as determined by the investigator, including but not limited to interstitial lung disease, non-infectious pneumonitis; uncontrolled diabetes, renal disease requiring dialysis, severe hepatic disease (Child-Pugh Class B or C), acute pancreatitis, etc.; 9) Patients with cardiovascular diseases of significant clinical relevance;
10) Patients with dysphagia, or gastrointestinal dysfunction or disease that could significantly affect the absorption of FS-207 tablets (e.g., severe ulcerative disease, poorly controlled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, etc.); 11) Patients with active autoimmune disease requiring systemic treatment, or a history of autoimmune disease with a potential for recurrence; 12) Patients with active Hepatitis B; active Hepatitis C; or Human Immunodeficiency Virus (HIV) infection; 13) Patients who have received a live vaccine or attenuated live vaccine within 4 weeks prior to the first dose of study medication; administration of inactivated vaccines is permitted; 14) Patients who have received treatment with other investigational drugs not yet approved for marketing, or who have participated in clinical trials involving interventional medical devices, within 4 weeks prior to the first dose of study medication; 15) Patients with active pulmonary tuberculosis (TB) (patients suspected of having active TB must undergo further evaluation by an infectious disease specialist to establish a definitive diagnosis) or a history of active TB; 16) Patients with any active infection requiring systemic treatment occurring within 2 weeks prior to the first dose of study medication; 17) Participants with a known or suspected history of severe allergic reactions to any component of the investigational drug, or a history of uncontrolled allergic asthma; 18) Patients who have previously undergone organ transplantation or allogeneic hematopoietic stem cell transplantation; 19) History of substance abuse, or known medical, psychological, or social conditions-such as a history of alcoholism or drug abuse; 20) Women who are pregnant or breastfeeding, or women of childbearing potential who have a positive pregnancy test result during the screening period; 21) Any other conditions that the investigator deems render the participant unsuitable for participation in this trial.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Part 1A
FS-207 monotherapy dose escalation
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FS-207 will be administered orally
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実験的：Part 1B
FS-207 monotherapy Dose expansion and optimization
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FS-207 will be administered orally
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
用量制限毒性（DLT）を有する参加者の数
時間枠：最大21日間
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最大21日間
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Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
時間枠：Up to 3 years
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Up to 3 years
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
RECIST v1.1による反応期間（DOR）
時間枠：最大5年間
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最大5年間
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RECIST v1.1による疾患制御率（DCR）
時間枠：最大5年間
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最大5年間
|
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RECIST v1.1による無増悪生存期間（PFS）
時間枠：最大5年間
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最大5年間
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RECIST v1.1による全生存期間（OS）
時間枠：最大5年間
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最大5年間
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Maximum Serum Concentration (Cmax) of FS-207
時間枠：up to 60 days
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up to 60 days
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Minimum Serum Concentration (Cmin) of FS-207
時間枠：Up to 60 days
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Up to 60 days
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Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of FS-207
時間枠：Up to 60 days
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Up to 60 days
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Time to Achieve Cmax (Tmax) of FS-207
時間枠：Up to 60 days
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Up to 60 days
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Confirmed Objective Response Rate(ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
時間枠：Up to 5 years
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Up to 5 years
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- ForesightTx
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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米国で製造され、米国から輸出された製品。
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