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临床试验/NCT05278364
NCT05278364招募中1 期

A Phase I/II, Open-Label, Single-arm, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antineoplastic Activity of SY-5007 in Patients With RET-altered Advanced Solid Tumor.

Shouyao Holdings (Beijing) Co. LTD2 个研究点 分布在 1 个国家目标入组 184 人开始时间: 2021年4月23日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
招募中
发起方
入组人数
184
试验地点
2
主要终点
Phase I: Determine the dose-limiting toxicities (DLT) during the first 28-day cycle of SY-5007 treatment
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a phase I/II, open-label, multi-center, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of SY-5007 administered orally to participants with advanced solid tumors, including RET Fusion-Positive NSCLC or RET-mutated MTC or other RET-altered advanced solid tumor.

详细描述

The study consists of 2 parts:

Part 1: Dose-escalation and dose-expansion in patients with RET Fusion-Positive NSCLC or RET-mutated MTC or other RET-altered advanced solid tumor. Dose-escalation study phase is designed to determine the DLTs (Dose-limiting toxicity) and recommended phase II dose (RP2D) and to characterize the safety, tolerability, and pharmacokinetics (PK) profile of SY-5007. Dose-expansion study phase is designed to evaluate the antitumor activity (ORR, DCR and DoR) of SY-5007 in patients.

Part 2: Phase II study to evaluate the antitumor efficacy of SY-5007. Patients with advanced RET Fusion-Positive NSCLC will be enrolled in this phase. SY-5007 will be administered orally 160mg twice daily in a 28-day cycle. This phase is designed to determine the antitumor activity (ORR, DCR, DoR, PFS and OS), safety, and PK of SY-5007.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •For Phase I:
  • •Male or female, at least 18 years of age.
  • •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to
  • •Estimated life expectancy >12 weeks.
  • •Patients must have at least one assessable lesion in dose-escalation part and one measurable lesion in dose-expansion part per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
  • •Dose-escalation Part: patients must have histological or cytological confirmed advanced solid tumours with RET alteration (fusion or mutation) and have progressed after standard therapy, or no standard or available curative therapy exists.
  • •Dose-expansion Part: Patients with advanced tumor must have histological or cytological confirmed RET alteration, including NSCLC patients with RET-fusion or MTC patients with RET-mutation or other patients with RET alteration, and either have progressed after standard therapy or no standard/ available curative therapy exists.
  • •Patients must have adequate organ function as defined in the below:
  • •Hepatic function:
  • •Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN) if no hepatic metastases are present, or otherwise ≤ 5 times ULN, Total serum bilirubin (TBIL) ≤ 1.5 times ULN.
  • •Bone marrow function (No blood transfusion or haematopoietic stimulating factor treatment within 10 days prior to testing):
  • •Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L; Platelets (PLT) count ≥ 75 x 10⁹/L; Hemoglobin (Hb) ≥ 85 g/L.
  • •Renal function:
  • •Creatinine clearance ≥ 50 mL/min.
  • •Coagulation function:
  • •Prothrombin time (PT) or International Normalized Ratio (INR) ≤ 1.5 times ULN.
  • •Serum lipid:
  • •Cholesterol ≤ 500mg/dL（12.92mmol/L）.
  • •Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the first dose, male and female patients of childbearing potential must be willing to completely abstain or agree to use an appropriate method of contraception during the entire study duration and for at least 3 months after the last dose of study medication.
  • •Willingness and ability to give informed consent and follow protocol procedures, and comply with follow-up visit requirements.
  • •For Phase II: As for phase I with the following modifications:
  • •Participants must have histological or cytological confirmed locally advanced or metastatic RET Fusion-Positive NSCLC, have progressed following platinum-based chemotherapy and/or PD-1/PD-L1 immunotherapy, or have not received prior systemic therapy, or in the opinion of the Investigator, they would be unlikely to tolerate or derive significant clinical benefit from appropriate standard of care therapy, or they declined standard therapy.
  • •The participants' tumor tissue or blood sample test results meet 1 of the following 2 criteria:
  • •Previous tumor tissue or blood sample confirmed positive for RET fusion by local laboratory.
  • •If no previous positive RET fusion test report is available, a compliant tumor tissue or blood sample must be tested at a central laboratory designated by the sponsor, using a second-generation sequencing (NGS)-based assay, and confirmed as positive for RET fusion.

排除标准

  • •Dose-expansion Part: Patient's cancer has a known primary driver alteration other than RET. e.g. EGFR, ALK, ROS1, KRAS, etc.
  • •Dose-expansion Part: Patients previously treated with a selective RET inhibitor.
  • •Patients received systemic antitumor therapy, including chemotherapy, radiotherapy, biologic therapy, endocrine therapy, or immunotherapy within 3 weeks prior to the first dose, except for the following:
  • •Nitrosoureas or mitomycin C within 6 weeks; Oral fluorouracils and small molecule drugs within 2 weeks or within 5 half-life periods of the drug (whichever is longer); Antitumour traditional Chinese medicine within 2 weeks.
  • •Patients received other unlisted clinical trial drugs or treatments within 4 weeks prior to the first dose.
  • •Patients underwent major organ surgery (excluding puncture biopsy) or had significant trauma within 4 weeks prior to the first dose.
  • •Adverse effects of previous anti-tumor therapy have not recovered to CTCAE 5.0 grade rating of ≤ grade 1 (except for toxicity judged by the investigator be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, etc.)
  • •Patients have symptomatic central nervous system (CNS) metastases, meningeal metastases, or a primary CNS tumor that is associated with progressive neurological symptoms.
  • •Patients with active uncontrolled systemic bacterial, viral, or fungal infection despite optimal treatment (chronic disease screening not required).
  • •Active hepatitis (Hepatitis B: HBsAg-positive and HBV-DNA ≥ 2000 IU/ mL; Hepatitis B: HCV antibody-positive and HCV-RNA ≥ 1000 IU/ml), HIV antibody-positive; Active syphilis.
  • •Patients have a history of severe cardiovascular disease, including but not limited to:
  • •Severe cardiac rhythm or conduction abnormalities, e.g. ventricular arrhythmia requiring clinical intervention, II-III degree atrioventricular block, etc.
  • •Mean QT interval corrected using Fridericia's formula (QTcF)> 480ms at rest. Acute coronary syndrome, congestive heart failure, aortic coarctation, stroke or other grade 3 or higher cardiovascular or cerebrovascular events within 6 months prior to the first dose.
  • •New York Heart Association (NYHA) ≥ class II heart failure or left ventricular ejection fraction (LVEF) < 50%.
  • •Hypertension remains uncontrolled after aggressive antihypertensive therapy.
  • •Patients have been treated with any CYP3A inhibitors or inducers within 14 days prior to the first dose.
  • •Patients with malignancies other than tumors treated in this study (except: malignancies that are cured and have not recurred within 3 years prior to study entry; completely resected basal cell and squamous cell skin cancer; completely resected carcinoma in situ of any type).
  • •Patients are unable to swallow the drug orally, or has a condition that seriously affects gastrointestinal absorption in the judgment of the investigator.
  • •For Phase II: As for phase I with the following modifications:
  • •Patients received any selective RET inhibitor (including marketed drugs such as selpercatinib, pralsetinib, and unmarketed experimental drugs).
  • •Patients have a history of hypersensitivity to any component or excipient of SY-5007 capsule.
  • •Patients participated in another clinical study within 4 weeks prior to the first dose or is scheduled to participate in another clinical study during the study period.
  • •Pregnant or breastfeeding female patients.
  • •Other conditions deemed by the investigator to be inappropriate for participation in this clinical trial.

研究组 & 干预措施

Dose-escalation and Dose-expansion

Experimental

Dose-escalation Phase:

Multiple doses of SY-5007 for oral administration.

Dose Expansion Phase:

RP2D of SY-5007 as determined during Dose Escalation.

干预措施: SY-5007 (Drug)

结局指标

主要结局

Phase I: Determine the dose-limiting toxicities (DLT) during the first 28-day cycle of SY-5007 treatment

时间窗: Dose-escalation Cycle 1 (each cycle is 28 days)

Maximum Tolerated Dose (MTD) and/or recommended phase 2 dose (RP2D) in Cycle 1

Phase I: Number of patients with adverse events and serious adverse events

时间窗: Up to 24 months

Characterization of the safety and tolerability

Phase II: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria

时间窗: Up to 24 months

Anti-tumor activity of SY-5007

次要结局

  • Phase I & II: Progression Free Survival (PFS)(Up to 24 months)
  • Phase I: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteriaOverall Response Rate (ORR) as assessed by RECIST 1.1 criteria(Up to 24 months)
  • Phase I & II: Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject)
  • Phase I & II: Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2) of SY-5007(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject)
  • Phase I & II: Overall survival (OS)(Up to 24 months)
  • Phase I & II: Disease control rate (DCR) as assessed by RECIST 1.1 criteria(Up to 24 months)
  • Phase I & II: Pharmacokinetic Parameters Including time to maximum plasma concentration (Tmax) of SY-5007(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject)
  • Phase I & II: Duration of response (DOR)(Up to 24 months)
  • Phase I & II: Percentage of Participants with any Serious Adverse Events (SAEs)(Up to 24 months)
  • Phase I & II: Pharmacokinetic Parameters Including Area Under the Plasma Concentration-Time Curve of SY-5007 (AUC)(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject)

研究者

发起方
Shouyao Holdings (Beijing) Co. LTD
申办方类型
Other
责任方
Sponsor

研究点 (2)

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