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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 september 2026 bijgewerkt door: 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

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

222

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm A: GFH276 + Cetuximab

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

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

Geneesmiddel: Cetuximab

Intravenous cetuximab at a dose of 500 mg/m²
Experimenteel: 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
Geneesmiddel: GFH276

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

Geneesmiddel: Nab paclitaxel

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

Geneesmiddel: Gemcitabine

Intravenous Gemcitabine at a dose of 1000 mg/m².
Experimenteel: 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.
Geneesmiddel: GFH276

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

Geneesmiddel: Fluorouracil

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

Geneesmiddel: Leucovorin

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

Geneesmiddel: Irinotecan

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

Geneesmiddel: Oxaliplatin

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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: up to 24 months

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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Phase II: Incidence and Severity of AE and SAE
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: up to 6 months

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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Genfleet Therapeutics (Shanghai) Inc.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 september 2026

Primaire voltooiing (Geschat)

1 november 2027

Studie voltooiing (Geschat)

1 september 2028

Studieregistratiedata

Eerst ingediend

9 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

24 juni 2026

Eerst geplaatst (Werkelijk)

1 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

5 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

30 september 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • GFH276X0201

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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