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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

30 septembre 2026 mis à jour par: 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

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

222

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • Australie
    • New South Wales
      • Concord, New South Wales, Australie, 2139
        • Pas encore de recrutement
        • Concord Cancer Centre, Concord Repatriation General Hospital, Sydney Local Health District
        • Contact:
      • North Ryde, New South Wales, Australie, 2109
        • Recrutement
        • Macquarie University / Clinical Trials Unit
        • Contact:
          • PhD
        • Contact:
    • South Australia
      • Woodville South, South Australia, Australie, 5011
        • Pas encore de recrutement
        • The Queen Elizabeth Hospital
        • Contact:
    • Victoria
      • Clayton, Victoria, Australie, 3168
        • Recrutement
        • Monash Health (Monash Medical Centre)
        • Contact:
      • Epping, Victoria, Australie, 3076
        • Pas encore de recrutement
        • Northern Health
        • Contact:
      • Frankston, Victoria, Australie, 3199
        • Recrutement
        • PASO Medical
        • Contact:
          • Vinod Ganju, MBBS
          • Numéro de téléphone: 0397815244
          • E-mail: vg@paso.com.au
  • Chine
    • Beijing Municipality
      • Beijing, Beijing Municipality, Chine, 100730
        • Recrutement
        • Peking Union Medical College Hospital
        • Contact:
          • Chunmei Bai, MD
    • Guangdong
      • Guangzhou, Guangdong, Chine, 510120
        • Recrutement
        • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
        • Contact:
          • Zhihua Li, MD
    • Heilongjiang
      • Harbin, Heilongjiang, Chine, 150081
        • Pas encore de recrutement
        • The Third Affiliated Hospital (Cancer Hospital) of Harbin Medical University
        • Contact:
          • Guangyu Wang, MD
    • Henan
      • Zhengzhou, Henan, Chine, 450052
        • Recrutement
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
          • Hong Zong, MD
    • Hubei
      • Wuhan, Hubei, Chine, 430022
        • Pas encore de recrutement
        • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
          • Heshui Wu, MD
    • Liaoning
      • Shenyang, Liaoning, Chine, 110001
        • Pas encore de recrutement
        • The First Affiliated Hospital of China Medical University
        • Contact:
          • Xiujuan Qu, MD
    • Shaanxi
      • Xi'an, Shaanxi, Chine, 710061
        • Pas encore de recrutement
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
          • Yinying Wu, MD
    • Shandong
      • Jinan, Shandong, Chine, 250117
        • Recrutement
        • Shandong First Medical University Affiliated Tumor Hospital
        • Contact:
          • Shuqin Ni, MD
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, Chine, 200032
        • Recrutement
        • Fudan University Shanghai Cancer Center
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, Chine, 610041
        • Recrutement
        • West China Hospital of Sichuan University
        • Contact:
          • Xuelei Ma, MD
    • Zhejiang
      • Hangzhou, Zhejiang, Chine, 310016
        • Recrutement
        • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
        • Contact:
          • Da Li, MD

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Arm A: GFH276 + Cetuximab

GFH276 once daily; cetuximab 500 mg/m² intravenous infusion every 2 weeks.
Médicament: GFH276

Oral GFH276 administered once daily in combination with other study drugs.

Médicament: Cetuximab

Intravenous cetuximab at a dose of 500 mg/m²
Expérimental: 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
Médicament: GFH276

Oral GFH276 administered once daily in combination with other study drugs.

Médicament: Nab paclitaxel

Intravenous nab-paclitaxel at a dose of 125 mg/m².

Médicament: Gemcitabine

Intravenous Gemcitabine at a dose of 1000 mg/m².
Expérimental: 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.
Médicament: GFH276

Oral GFH276 administered once daily in combination with other study drugs.

Médicament: Fluorouracil

Intravenous Fluorouracil at a dose of 2400 mg/m² via 46-hour infusion.Dosing may follow the above regimen or local institutional standards.

Médicament: Leucovorin

Intravenous leucovorin at a dose of 400 mg/m².Dosing may follow the above regimen or local institutional standards.

Médicament: Irinotecan

Intravenous irinotecan at a dose of 150 mg/m².Dosing may follow the above regimen or local institutional standards.

Médicament: Oxaliplatin

Intravenous oxaliplatin at a dose of 85 mg/m².Dosing may follow the above regimen or local institutional standards.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Délai: 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)
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: up to 24 months

Number of participants with abnormality incorrected QT interval using Frederica's formula (QTcF)
up to 24 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Phase II: Incidence and Severity of AE and SAE
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
OS
Délai: From the first dose until date of death from any cause, assessed up to 24 months

Overall Survival
From the first dose until date of death from any cause, assessed up to 24 months
Time to peak plasma concentration（Tmax） of GFH276
Délai: 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
Délai: 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
Délai: up to 6 months

Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including AUC0-24 were evaluated.
up to 6 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Genfleet Therapeutics (Shanghai) Inc.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 septembre 2026

Achèvement primaire (Estimé)

1 novembre 2027

Achèvement de l'étude (Estimé)

1 septembre 2028

Dates d'inscription aux études

Première soumission

9 juin 2026

Première soumission répondant aux critères de contrôle qualité

24 juin 2026

Première publication (Réel)

1 juillet 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

5 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

30 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • GFH276X0201

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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