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A Study to Evaluate GFH375 Versus Docetaxel in Participants With Non-Small Cell Lung Cancer With KRAS G12D Mutation

2026年8月5日 更新者：Genfleet Therapeutics (Shanghai) Inc.

A Phase III, Randomized, Open-Label, Multicenter Study to Evaluate GFH375 Versus Docetaxel in Participants With Locally Advanced and Unresectable or Metastatic Non-Small Cell Lung Cancer With KRAS G12D Mutation Failed Prior Standard Therapy

The purpose of this study is to compare the effectiveness, safety and tolerability of GFH375 versus docetaxel in participants with KRAS G12D-mutant non-small cell lung cancer (NSCLC).

GFH375 is an oral, highly selective, non-covalent small-molecule inhibitor targeting the KRAS G12D mutation. Preclinical studies showed GFH375 strongly blocks KRAS-driven signaling and cancer cell growth, and demonstrated anti-tumor activity in NSCLC animal models. Docetaxel is a chemotherapy drug for locally advanced or metastatic NSCLC.

This is an open-label, randomized controlled trial. Both participant and study doctor will know which study medication each participant receives.

After enrollment, participant will be randomly assigned to either the GFH375 group or docetaxel group by chance. Neither participant nor study doctor can pick your treatment group. You have a two-thirds chance to receive GFH375 and a one-third chance to receive docetaxel.

  • GFH375 group: Take GFH375 tablets by mouth once daily as scheduled; each treatment cycle lasts 21 days.
  • Docetaxel group: Receive docetaxel via intravenous infusion at 75 mg/m² once every 3 weeks.

Study treatment will continue until cancer gets worse, participant can't tolerate the study treatment, or other conditions make participant unable to keep receiving study treatment.

Some participants on docetaxel may be able to switch to GFH375 during the study if their cancer becomes worse. There will be safety checks at each visit, and the doctors will continue to check for medical problems and participant 's wellbeing throughout the study. Participants will continue to have scans of their tumor every 6 weeks for the first year, then every 9 weeks until their cancer becomes worse. After participant's cancer becomes worse, clinic staff will telephone participant every 3 mouths to check on their cancer.

調査の概要

状態

募集

条件

介入・治療

研究の種類

介入

入学 (推定)

300

段階

  • フェーズ 3

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

  • 中国
    • Shanghai Municipality
      • Shanghai、Shanghai Municipality、中国、201210
        • 募集
        • Shanghai Lung Cancer Center, Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
        • コンタクト：

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. Voluntary participation in the study and signed informed consent form (ICF).
  • 2. Age ≥ 18 years at the time of signing the ICF; male or female.
  • 3. Histologically or cytologically confirmed locally advanced unresectable or metastatic non small cell lung cancer (NSCLC).
  • 4. Participants must provide adequate and qualified tumor tissue slides samples or agree to undergo tumor biopsy to obtain tissue samples for central laboratory confirmation of KRAS G12D mutation.
  • 5. Disease progression or intolerance to toxicity after at least one prior line of platinum based chemotherapy and anti PD 1/PD L1 antibody therapy.
  • 6. At least one measurable target lesion according to RECIST version 1.1.
  • 7. Investigator assessed life expectancy ≥ 12 weeks.
  • 8. Adequate organ function.
  • 9. Ability to communicate well, comply with scheduled follow up visits, and adhere to protocol requirements.

Exclusion Criteria:

  • 1. Presence of other driver gene mutations in NSCLC, or concurrent other KRAS or RAS mutations.
  • 2. Other malignancy that has progressed or required treatment within 3 years prior to randomization.
  • 3. Leptomeningeal metastasis, or symptomatic or progressive central nervous system (CNS) metastasis.
  • 4. Existing or potential severe bone injury due to bone metastasis, or uncontrolled pain related to bone metastasis.
  • 5. Prior treatment with KRAS G12D targeted therapy or pan RAS/KRAS targeted therapy.
  • 6. Prior treatment with docetaxel as part of systemic therapy.
  • 7. Radiotherapy within 4 weeks prior to randomization, or other local anti tumor therapy within 4 weeks prior to randomization.
  • 8. Other anti tumor therapy within 28 days or 5 half lives prior to randomization, or cell therapy within 3 months prior to randomization.
  • 9. Clinically significant severe cardiovascular disease.
  • 10. Stroke or other severe cerebrovascular disease within 6 months prior to randomization.
  • 11. Major acute or chronic infectious disease.
  • 12. Other poorly controlled systemic diseases.
  • 13. Severe psychiatric or psychological disorder, or history of drug abuse, or severe alcohol abuse.
  • 14. Pregnancy or breastfeeding.
  • 15. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.

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：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：GFH375 group
Participants will take GFH375 orally once daily of every 21-day cycle.
薬：GFH375
GFH375 administered orally at the protocol-specified dose once daily. Each treatment cycle is 21 days.
アクティブコンパレータ：Docetaxel group
Participants will receive docetaxel on day 1 of every 21-day cycle.
薬：Docetaxel
Receive docetaxel via intravenous infusion at 75 mg/m² 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
Objective Response Rate(ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR)
時間枠：From the first dose until the date of first documented CR or PR, assessed up to 24 months
ORR is the proportion of participants whose best response is either complete response (CR) or partial response (PR) per RECIST v1.1 assessed by BICR.
From the first dose until the date of first documented CR or PR, assessed up to 24 months
Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR)
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.
PFS is defined as the time from the date of randomization until the date of documented radiographic disease progression per RECIST v1.1, as assessed by BICR or until death due to any cause, whichever comes first.
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.
Overall Survival (OS)
時間枠：From the first dose until the date of death from any cause, whichever came first, assessed up to 36~48 months
OS is defined as the time from the date of randomization until the date of death from any cause.
From the first dose until the date of death from any cause, whichever came first, assessed up to 36~48 months

二次結果の測定

結果測定
メジャーの説明
時間枠
Objective Response Rate (ORR) per RECIST v1.1, as assessed by the investigator
時間枠：From the first dose until the date of first documented CR or PR,assessed up to 24 months.
ORR is defined as the proportion of participants whose best overall response (BOR) is rated as confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1. as assessed by the investigator.
From the first dose until the date of first documented CR or PR,assessed up to 24 months.
PFS per RECIST v1.1. as assessed by the investigator
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.
PFS is defined as the time from the date of randomization until the date of documented radiographic disease progression per RECIST v1.1 as assessed by the investigator or until death due to any cause, whichever comes first.
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.
DCR per RECIST v 1.1 as assessed by the investigator and the BICR
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.
DCR is defined as the proportion of participants whose best overall response is rated as CR, confirmed PR or SD per RECIST v1.1 as assessed by the investigator and the BICR.
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 per RECIST v 1.1 as assessed by the investigator and the BICR
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.
DOR is defined as the time from the date of first documented response (CR or PR subsequently confirmed) to the date of first documented PD per RECIST v1.1 as assessed by the investigator and the BICR or death due to any cause, whichever occurs first.
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 per RECIST v 1.1 as assessed by the investigator and the BICR
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.
TTR is defined as the time from the date of randomization to the first documentation of objective response (confirmed CR or confirmed PR) per RECIST v1.1. as assessed by the investigator and the BICR.
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.
Number of Participants with Adverse Events (AEs)
時間枠：From the first dose until 30 days after the last dose, assessed up to 24 months.
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
From the first dose until 30 days after the last dose, assessed up to 24 months.
Severity of Adverse Events(AEs)
時間枠：From the first dose until 30 days after the last dose, assessed up to 24 months.
The severity of an adverse event is commonly graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE )5.0.
From the first dose until 30 days after the last dose, assessed up to 24 months.
Incidence of AEs that result in treatment discontinuation, treatment interruption, or dose reduction.
時間枠：From the first dose until 30 days after the last dose, assessed up to 24 months.
AEs that result in treatment discontinuation, treatment interruption, or dose reduction.
From the first dose until 30 days after the last dose, assessed up to 24 months.
Severity of adverse events (AEs) leading to treatment discontinuation, treatment interruption, and dose reduction.
時間枠：From the first dose until 30 days after the last dose, assessed up to 24 months.
Severity of adverse events (AEs) leading to treatment discontinuation, treatment interruption, and dose reduction per CTCAE 5.0.
From the first dose until 30 days after the last dose, assessed up to 24 months.
Time to deterioration in NSCLC symptoms evaluated via European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) items
時間枠：From the first dose until 30 days after the last dose, assessed up to 24 months.
Time to deterioration is defined as time between randomization and the first occurrence of a meaningful deterioration in the corresponding EORTC QLQ-LC13 items score compared with the baseline score. EORTC QLQ-LC13 is a lung-cancer specific module that serves as an additional 13 item questionnaire to the general EORTC cancer questionnaire. It consists of 3 items to assess dyspnea, and 10 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. Scores range from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems.
From the first dose until 30 days after the last dose, assessed up to 24 months.
Time to Worsening measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) items
時間枠：From the first dose until 30 days after the last dose, assessed up to 24 months.
Time to Worsening is defined as time between randomization and the first occurrence of a meaningful worsening in the composite EORTC QLQ-C30 items scores compared with the baseline score. EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.
From the first dose until 30 days after the last dose, assessed up to 24 months.
Change from baseline in EORTC QLQ-C30
時間枠：From the first dose to week12.
The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.
From the first dose to week12.
Change from baseline in EORTC QLQ-LC13
時間枠：From the first dose to week12.
EORTC QLQ-LC13 is a lung-cancer specific module that serves as an additional 13 item questionnaire to the general EORTC cancer questionnaire. It consists of 3 items to assess dyspnea, and 10 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. Scores range from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems.
From the first dose to week12.
Pharmacokinetics (PK) of GFH375: Trough concentration after multiple dosing
時間枠：From the first dose to Cycle 6 Day 1(each cycle is 21 days).
Trough concentration will be recorded from plasma samples collected.
From the first dose to Cycle 6 Day 1(each cycle is 21 days).
PK of GFH375: Peak concentration after multiple dosing
時間枠：From the first dose to Cycle 6 Day 1(each cycle is 21 days).
Peak concentration will be recorded from plasma samples collected.
From the first dose to Cycle 6 Day 1(each cycle is 21 days).

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.

捜査官

  • 主任研究者：Shun Lu, MD、Shanghai Lung Cancer Center, Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine

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 (実際)

2026年7月27日

一次修了 (推定)

2030年6月30日

研究の完了 (推定)

2031年4月30日

試験登録日

最初に提出

2026年6月15日

QC基準を満たした最初の提出物

2026年6月23日

最初の投稿 (実際)

2026年6月25日

学習記録の更新

投稿された最後の更新 (実際)

2026年8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8月5日

最終確認日

2026年8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

  • GFH375X1303

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

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いいえ

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いいえ

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