A Phase III Study to Evaluate the Efficacy and Safety of JYP0322 in Previously Untreated ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
A Randomized, Open-Label, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of JYP0322 Versus Crizotinib in Previously Untreated ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ 3
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:
- Voluntary participation and signed written informed consent (ICF) before any study-specific procedure.
Age ≥ 18 years at screening. Histologically or cytologically confirmed, unresectable locally advanced (AJCC 9th edition stage IIIB or IIIC not amenable to multimodality therapy) or metastatic (stage IV) ROS1-positive non-small cell lung cancer (NSCLC).
ROS1 gene rearrangement/fusion positivity confirmed by a qualified local laboratory using PCR, NGS, or FISH. IHC alone is not acceptable. A written report of the ROS1 test must be provided.
Sufficient and adequate archival tumor tissue must be available for central laboratory ROS1 retesting per the Central Lab Manual; if no archival tissue is available, a fresh tumor biopsy is required.
No prior ROS1 TKI therapy. Prior systemic therapy limited to ≤1 line of standard chemotherapy:
A prior chemotherapy-based regimen administered for ≥1 cycle counts as one line.
Disease recurrence within 6 months after completion of adjuvant chemotherapy counts that adjuvant regimen as one prior line.
Asymptomatic central nervous system (CNS) metastases allowed (leptomeningeal carcinomatosis excluded). Previously treated and controlled/stabilized CNS metastases permitted if:
On non-enzyme-inducing antiepileptic drugs (non-EIAED) for seizure prophylaxis; or EIAED discontinued ≥14 days before randomization.
If corticosteroids needed, stable or tapering dose ≤10 mg/day prednisone (or equivalent) for ≥14 days before randomization.
Prior local therapy (WBRT, SRS/SRT) completed ≥14 days before randomization; treatment-related toxicities (except alopecia) resolved to ≤ Grade 1 (CTCAE v5.0).
At least one measurable lesion per RECIST v1.1. ECOG performance status 0-1. Expected survival ≥ 3 months.
Adequate organ function within 14 days before randomization (no blood products, growth factors, or platelet/ WBC boosters within 14 days):
- ANC ≥ 1.5 × 10^9/L
- Platelets ≥ 100 × 10^9/L
- Hemoglobin ≥ 90 g/L (stable erythropoietin ≥3 months allowed)
- CrCl > 45 mL/min (Cockcroft-Gault)
- Total bilirubin < 1.5 × ULN (Gilbert syndrome ≤ 3.0 × ULN)
- AST and ALT < 2.5 × ULN (< 5 × ULN if liver metastasis)
- APTT and INR < 1.5 × ULN Women of childbearing potential: negative serum pregnancy test within 7 days before randomization. All participants with reproductive potential (male and female) must agree to use highly effective contraception (hormonal, barrier, or abstinence) during treatment and for 6 months after last dose. Willing and able to comply with scheduled visits, treatment, labs, and procedures.
Exclusion Criteria:
- History of severe cardiovascular or cerebrovascular disease, including but not limited to: clinically significant cardiac rhythm or conduction abnormality (e.g., ventricular arrhythmia requiring intervention, 2nd-3rd degree AV block); acute coronary syndrome, congestive heart failure, aortic dissection, severe stable/unstable angina, coronary/peripheral vascular intervention, stroke or other ≥Grade 3 cerebrovascular event (including TIA), pulmonary embolism, DVT or other clinically significant thrombosis within 6 months before randomization; NYHA > Class II heart failure or LVEF < 50%; any uncontrolled atrial fibrillation; QTcF > 470 ms or symptomatic bradycardia < 45 bpm; known congenital long QT syndrome or history of QT prolongation.
Active infection requiring IV antibiotics or hospitalization at randomization. Acute flare of dysphagia or GI disease affecting absorption (Crohn's, UC, short bowel syndrome, or other malabsorption).
Failure to recover from prior antitumor therapy toxicity to baseline or ≤Grade 1 (CTCAE v5.0), except alopecia, Grade 2 peripheral neuropathy, or hypothyroidism controlled by replacement judged safe by investigator.
Major surgical procedure (other than dx/biopsy/drainage) within 4 weeks before randomization, or anticipated major surgery during study; vascular access placement and minor procedures (catheter, core needle biopsy) allowed.
Other primary malignancy except: adequately treated melanoma/skin carcinoma/cervical carcinoma in situ; treated non-metastatic prostate cancer; or other primary malignancy with no relapse ≥3 years.
Untreated spinal cord compression by tumor. Participated in another interventional trial within 4 weeks before first dose (screen failures exempt).
Interstitial fibrosis, ILD, or drug-induced pneumonitis within 6 months before first dose not recovered to Grade 1 (asymptomatic radiation pneumonitis exempt).
Systemic anticancer therapy (chemo-based or other) within 14 days or 5 half-lives (whichever shorter, minimum 14 days) before randomization.
Clinically uncontrolled serous effusion needing drainage > once/month (pericardial/pleural/ascites), or < 2 weeks observation after last drainage before randomization.
History of severe allergy or hypersensitivity to JYP0322 or crizotinib excipients.
Active HBV (HBsAg+ and HBV DNA ≥1000 IU/mL or 5000 copies/mL), active HCV (RNA+), syphilis requiring treatment (RPR ≤1:2 with TPHA+ allowed), or HIV infection.
Pregnant or lactating. Use of strong CYP3A4 inhibitors/inducers or narrow-therapeutic-index CYP3A4 substrates within 14 days or 5 half-lives (shorter) before randomization, or inability to discontinue during study.
Active or recurrent autoimmune disease, depression/affective disorder or suicidal risk, prior bone marrow/organ transplant, or any condition investigator judges unsafe.
Uncontrolled hyperthyroidism or hypothyroidism with prior severe comorbidity. Moderate-to-severe hepatic impairment history: prior ≥Grade 3 hepatotoxicity, or serious liver baseline (cirrhosis etc.).
Tumor invasion of great vessels (aorta, pulmonary artery/vein, vena cava) on imaging; OR any prior TKI therapy including ROS1-TKI.
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：ランダム化
- 介入モデル：並列代入
- 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 |
|---|---|
|
実験的：JYP0322 Tablets
|
Oral administration, 150 mg each dose, three times daily (TID), continuous dosing.
|
|
アクティブコンパレータ：Crizotinib Capsules
|
Oral administration, 250 mg twice daily (BID), continuous dosing.
|
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR/BIRC) per RECIST v1.1
時間枠：From randomization to the date of first documented radiographic disease progression or death from any cause, whichever occurs first, assessed up to approximately 24 months
|
PFS is defined as the time from randomization to the first occurrence of radiographic disease progression determined by blinded independent central review (BIRC) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death due to any cause within 12 weeks after last tumor assessment (to avoid censoring death as non-event if no progression documented).
Patients alive and without progression at data cutoff are censored at the date of last adequate tumor assessment.
|
From randomization to the date of first documented radiographic disease progression or death from any cause, whichever occurs first, assessed up to approximately 24 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Investigator-assessed Progression-Free Survival (PFS) per RECIST v1.1
時間枠：From randomization to first documented radiographic progression by investigator or death from any cause, whichever occurs first, assessed up to ~24 months
|
PFS assessed by the local investigator using the same RECIST v1.1 criteria and scan schedule as the BIRC pathway, but without blinding to treatment assignment.
Defined as time from randomization to first investigator-determined radiographic disease progression, or death from any cause (if no prior progression).
No central adjudication.
Used for sensitivity analysis against the primary BIRC-based PFS.
|
From randomization to first documented radiographic progression by investigator or death from any cause, whichever occurs first, assessed up to ~24 months
|
|
Overall Survival (OS)
時間枠：From randomization to date of death from any cause, assessed up to approximately 36 months (or final analysis cut-off)
|
OS is defined as the time from randomization to the date of death due to any cause.
Patients alive at the time of data cutoff will be censored at the last known alive date.
OS will be estimated using the Kaplan-Meier method and compared between arms by log-rank test; hazard ratio and 95% CI from Cox proportional hazards model reported.
|
From randomization to date of death from any cause, assessed up to approximately 36 months (or final analysis cut-off)
|
|
Incidence, severity, and relationship of Adverse Events (AEs) and Serious Adverse Events (SAEs)
時間枠：From first dose of study drug to 30 days after last dose (or 90 days for SAEs / death), assessed up to ~24 months
|
From first dose of study drug to 30 days after last dose (or 90 days for SAEs / death), assessed up to ~24 months
|
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
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