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A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation

2026年7月9日 更新者：Genfleet Therapeutics (Shanghai) Inc.

A Multi-center, Open-label Phase Ib/II Study Exploring the Safety/Tolerability, Pharmacokinetics, and Efficacy of GFH276 in Combination With Cetuximab or Chemotherapy in the Treatment of Patients With Advanced Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation

A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

This is an open-label, multicenter Phase Ib/II clinical trial to evaluate the safety, tolerability, and preliminary anti-tumor efficacy of oral GFH276 in combination with cetuximab or standard chemotherapy in adult patients with locally advanced or metastatic RAS-mutated solid tumors and pancreatic ductal adenocarcinoma (PDAC).

Participants will be enrolled into three treatment arms with different combination regimens.

In the Phase Ib stage, dose escalation of GFH276 will be performed in each combination arm to identify the optimal recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, Phase II expansion cohorts will enroll eligible patients 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

介入

入学 (推定)

222

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

  • オーストラリア
    • New South Wales
      • Concord、New South Wales、オーストラリア、2139
        • Concord Cancer Centre, Concord Repatriation General Hospital, Sydney Local Health District
        • コンタクト：
          • Kim Tam B Bui, MBBS
      • North Ryde、New South Wales、オーストラリア、2109
        • Macquarie University / Clinical Trials Unit
        • コンタクト：
          • PhD
        • コンタクト：
          • Andrew Parsonson, PhD
    • South Australia
      • Woodville South、South Australia、オーストラリア、5011
        • The Queen Elizabeth Hospital
        • コンタクト：
          • Timothy Price, MBBS
    • Victoria
      • Clayton、Victoria、オーストラリア、3168
        • Monash Health (Monash Medical Centre)
      • Epping、Victoria、オーストラリア、3076
        • Northern Health
        • コンタクト：
          • Belinda Lee, MBBS
      • Frankston、Victoria、オーストラリア、3199
        • PASO Medical
        • コンタクト：
          • Vinod Ganju, MBBS
  • 中国
    • Beijing Municipality
      • Beijing、Beijing Municipality、中国、100730
        • Peking Union Medical College Hospital
        • コンタクト：
          • Chunmei Bai, MD
    • Guangdong
      • Guangzhou、Guangdong、中国、510120
        • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
        • コンタクト：
          • Zhihua Li, MD
    • Heilongjiang
      • Harbin、Heilongjiang、中国、150081
        • The Third Affiliated Hospital (Cancer Hospital) of Harbin Medical University
        • コンタクト：
          • Guangyu Wang, MD
    • Henan
      • Zhengzhou、Henan、中国、450052
        • The First Affiliated Hospital of Zhengzhou University
        • コンタクト：
          • Hong Zong, MD
    • Hubei
      • Wuhan、Hubei、中国、430022
        • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • コンタクト：
          • Heshui Wu, MD
    • Liaoning
      • Shenyang、Liaoning、中国、110001
        • The First Affiliated Hospital of China Medical University
        • コンタクト：
          • Xiujuan Qu, MD
    • Shaanxi
      • Xi'an、Shaanxi、中国、710061
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • コンタクト：
          • Yinying Wu, MD
    • Shandong
      • Jinan、Shandong、中国、250117
        • Shandong First Medical University Affiliated Tumor Hospital
        • コンタクト：
          • Shuqin Ni, MD
    • Shanghai Municipality
      • Shanghai、Shanghai Municipality、中国、200032
        • Fudan University Shanghai Cancer Center
        • コンタクト：
    • Sichuan
      • Chengdu、Sichuan、中国、610041
        • West China Hospital of Sichuan University
        • コンタクト：
          • Xuelei Ma, MD
    • Zhejiang
      • Hangzhou、Zhejiang、中国、310016
        • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
        • コンタクト：
          • Da Li, MD

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

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

いいえ

説明

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Histologically or cytologically confirmed locally advanced or metastatic solid tumor and PDAC with RAS mutation or KRAS amplification
  3. At least one measurable lesion according to RECIST v1.1
  4. ECOG performance status 0 or 1
  5. Life expectancy > 3 months
  6. Adequate organ function
  7. Willing to provide written informed consent
  8. Fertile participants must use effective contraception

Exclusion Criteria:

  1. Other active malignancy within 3 years
  2. Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
  3. History of active clinically significant cardiovascular dysfunction
  4. For participants with known concomitant second oncodriver for PDAC or for solid tumors.
  5. With active infection (HIV, HBV, HCV, syphilis)
  6. The presence of clinical or radiological evidence of intestinal obstruction.
  7. Prior anticancer therapy within 28 days or 5 half-lives
  8. Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months
  9. Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
  10. History of central nervous system (CNS)disease
  11. Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
  12. With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

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：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：Arm A: GFH276 + Cetuximab
GFH276 once daily; cetuximab 500 mg/m² intravenous infusion every 2 weeks.
薬：GFH276
Oral GFH276 administered once daily in combination with other study drugs.
薬：Cetuximab
Intravenous cetuximab at a dose of 500 mg/m²
実験的：Arm B: GFH276 + AG
GFH276 once daily; nab-paclitaxel 125 mg/m² + gemcitabine 1000 mg/m² (AG regimen); 4-week cycle (D1, D8, D15) or 3-week cycle (D1, D8) in China
薬：GFH276
Oral GFH276 administered once daily in combination with other study drugs.
薬：Nab paclitaxel
Intravenous nab-paclitaxel at a dose of 125 mg/m².
薬：Gemcitabine
Intravenous Gemcitabine at a dose of 1000 mg/m².
実験的：Arm C: GFH276 + mFOLFIRINOX

GFH276 once daily; mFOLFIRINOX :Fluorouracil 2400 mg/m²(46 h), Leucovorin 400 mg/m², Irinotecan 150 mg/m², Oxaliplatin 85 mg/m², IV D1, every 2 weeks .

The mFOLFIRINOX regimen may be administered per the above dosage, or in accordance with national or institutional guidelines.
薬：GFH276
Oral GFH276 administered once daily in combination with other study drugs.
薬：Fluorouracil
Intravenous Fluorouracil at a dose of 2400 mg/m² via 46-hour infusion.Dosing may follow the above regimen or local institutional standards.
薬：Leucovorin
Intravenous leucovorin at a dose of 400 mg/m².Dosing may follow the above regimen or local institutional standards.
薬：Irinotecan
Intravenous irinotecan at a dose of 150 mg/m².Dosing may follow the above regimen or local institutional standards.
薬：Oxaliplatin
Intravenous oxaliplatin at a dose of 85 mg/m².Dosing may follow the above regimen or local institutional standards.

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 28 days (21 days for AG （3-week cycle）)
The incidence of DLT events
First 28 days (21 days for AG （3-week cycle）)
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 24 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 24 months
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 24 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 24 months
Phase Ib: Number of participants with abnormality in hematology laboratory parameters
時間枠：up to 24 months
Number of participants with abnormality in hematology laboratory parameters，Hematology assessments will include hemoglobin, white blood cell count, differential white blood cell counts and platelet count
up to 24 months
Phase Ib: Number of participants with abnormality in clinical chemistry laboratory assessments
時間枠：up to 24 months
Number of participants with abnormality in clinical chemistry laboratory assessments， assessments will include serum chemistry (such as sodium, potassium, urea, creatinine) and liver function parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin.
up to 24 months
Phase Ib: Number of participants with abnormality in body temperature
時間枠：up to 24 months
Number of participants with abnormality in body temperature(°C), throughout the study.
up to 24 months
Phase Ib: Number of participants with abnormality in blood pressure
時間枠：up to 24 months
Number of participants with abnormality in blood pressure, including systolic blood pressure (mmHg) and diastolic blood pressure (mmHg)
up to 24 months
Phase Ib: Number of participants with abnormality in Physical Examination Findings
時間枠：up to 24 months
Number of participants with abnormality in Physical Examination Findings
up to 24 months
Phase Ib: Number of participants with abnormality in PR interval
時間枠：up to 24 months
Number of participants with abnormality in electrocardiogram (ECG) parameters, including PR interval
up to 24 months
Phase Ib: Number of participants with abnormality in corrected QT interval using Frederica's formula (QTcF)
時間枠：up to 24 months
Number of participants with abnormality incorrected QT interval using Frederica's formula (QTcF)
up to 24 months

二次結果の測定

結果測定
メジャーの説明
時間枠
OS
時間枠：最初の投与から、いかなる原因による死亡日まで、最大24か月間評価
全生存期間
最初の投与から、いかなる原因による死亡日まで、最大24か月間評価
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 24 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 24 months
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 24 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 24 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 24 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 24 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 24 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 24 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 24 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 24 months
Time to peak plasma concentration（Tmax） of GFH276
時間枠：up to 6 months
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Tmax were evaluated.
up to 6 months
Maximum plasma concentration of GFH276
時間枠：up to 6 months
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Cmax were evaluated.
up to 6 months
Area Under the Curve from time zero to 24 hours of GFH276
時間枠：up to 6 months
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including AUC0-24 were evaluated.
up to 6 months

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Genfleet Therapeutics (Shanghai) Inc.

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年9月1日

一次修了 (推定)

2027年11月1日

研究の完了 (推定)

2028年9月1日

試験登録日

最初に提出

2026年6月9日

QC基準を満たした最初の提出物

2026年6月24日

最初の投稿 (実際)

2026年7月1日

学習記録の更新

投稿された最後の更新 (実際)

2026年7月10日

QC基準を満たした最後の更新が送信されました

2026年7月9日

最終確認日

2026年7月1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

  • GFH276X0201

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?

いいえ

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

いいえ

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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