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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 uppdaterad av: 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

Studieöversikt

Status

Rekrytering

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Beräknad)

222

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Arm A: GFH276 + Cetuximab

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

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

Läkemedel: Cetuximab

Intravenous cetuximab at a dose of 500 mg/m²
Experimentell: 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
Läkemedel: GFH276

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

Läkemedel: Nab paclitaxel

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

Läkemedel: Gemcitabine

Intravenous Gemcitabine at a dose of 1000 mg/m².
Experimentell: 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.
Läkemedel: GFH276

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

Läkemedel: Fluorouracil

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

Läkemedel: Leucovorin

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

Läkemedel: Irinotecan

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

Läkemedel: Oxaliplatin

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

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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)
Tidsram: up to 24 months

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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Phase II: Incidence and Severity of AE and SAE
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: up to 6 months

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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Genfleet Therapeutics (Shanghai) Inc.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Beräknad)

1 september 2026

Primärt slutförande (Beräknad)

1 november 2027

Avslutad studie (Beräknad)

1 september 2028

Studieregistreringsdatum

Först inskickad

9 juni 2026

Först inskickad som uppfyllde QC-kriterierna

24 juni 2026

Första postat (Faktisk)

1 juli 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

5 oktober 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

30 september 2026

Senast verifierad

1 september 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • GFH276X0201

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

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