This is a Multicenter, Open-label, Phase I/II Study to Explore the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Efficacy of GFH276 in Patients With Advanced NSCLC Harboring a RAS Mutation. (GFH276X1203)
A Phase Ib/II, Multicenter, Open-Label Study To Evaluate Safety, Efficacy And Pharmacokinetics Of GFH276 In Combination With Tislelizumab, Pemetrexed And Platinum (Carboplatin Or Cisplatin) As First-Line Therapy In Participants With Locally Advanced Or Metastatic Non-Squamous Non-Small-Cell Lung Cancer Harboring RAS Mutation
This is an open-label, multicenter Phase Ib/II clinical study evaluating GFH276 in combination with tislelizumab plus pemetrexed/platinum based regimen as first-line therapy in participants with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) harboring RAS mutation or KRAS amplification.
調査の概要
状態
詳細な説明
This open-label, multicenter Phase Ib/II study enrolls participants with locally advanced or metastatic non-squamous NSCLC with RAS mutation or KRAS amplification, who have not received prior systemic anti-cancer therapy for advanced disease.
In Phase Ib, dose escalation of GFH276 will be performed in assigned arm to identify the recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, participants will be enrolled in Phase II to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.
Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Li Bai
- 電話番号：+86 2168821388
- メール：lbai@genfleet.com
研究連絡先のバックアップ
- 名前：Pingping Zhang
- 電話番号：+86 2168821388
- メール：ppzhang@genfleet.com
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Histologically/cytologically confirmed locally advanced or metastatic non squamous NSCLC (AJCC 8th edition Stage IIIB-IV).
- Confirmed RAS mutation or KRAS amplification；tumor cell PD L1 test report available
- No prior systemic anti-tumor therapy for advanced disease
- At least 1 measurable lesion outside the central nervous system (CNS) per RECIST v1.1
- ECOG performance status 0 or 1
- Life expectancy>3 months
- Willing to provide written informed consent
- Fertile participants must use effective contraception
- Adequate organ function
Exclusion Criteria:
- Other active malignancy within 3 years
- Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- History of active clinically significant cardiovascular dysfunction
- Known to harbor other targetable driver gene alterations
- Presence of active infection (HIV, HBV, HCV,)
- Prior anti-tumor therapy within 28 days or 5 half-lives
- Diagnosis of unstable thrombotic events requiring therapeutic intervention within 3 months prior to the first dose of study treatment.
- Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
- History of central nervous system (CNS)disease
- Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
- With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.
- Active autoimmune disease requiring systemic treatment.
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：なし
- 介入モデル：単一グループの割り当て
- 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 |
|---|---|
|
実験的：GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks |
Oral GFH276, administered at specified dose on schedule. Tislelizumab 200 mg, intravenous infusion, once every 3 weeks.or without Tislelizumab Pemetrexed 500 mg/m², intravenous infusion, once every 3 weeks. Cisplatin 75 mg/m², intravenous infusion, once every 3 weeks. Carboplatin at AUC=5, intravenous infusion, once every 3 weeks. |
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 |
|---|---|---|
|
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
時間枠：First 21 days
|
The incidence of DLT events |
First 21 days
|
|
Phase II:Objective Response Rate (ORR)
時間枠：From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Assessed by investigators according to RECIST 1.1 |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
時間枠：From the first dose until 30 days after the last dose, assessed up to 36 months
|
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0 |
From the first dose until 30 days after the last dose, assessed up to 36 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
DCR
時間枠：From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Disease Control Rate (DCR) |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
DoR
時間枠：From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Duration of Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
TTR
時間枠：From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Time To Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
PFS
時間枠：From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Progression-Free Survival (PFS) per Response Evaluation Criteria according to RECIST 1.1, as Determined by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
OS
時間枠：From the first dose until date of death from any cause, assessed up to 36 months
|
Overall Survival |
From the first dose until date of death from any cause, assessed up to 36 months
|
|
Phase II: Incidence and Severity of AE and SAE
時間枠：From the first dose until 30 days after the last dose, assessed up to 36 months
|
Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0 |
From the first dose until 30 days after the last dose, assessed up to 36 months
|
協力者と研究者
捜査官
- 主任研究者：Ziming Li, MD、Shanghai Chest Hospital
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
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- GFH276X1203
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?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
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