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

NCT07678593 | Not Yet Recruiting Phase 1

• 1 other identifier: GFH276X0201
• Study Type: interventional
• Target: 222
• Locations: 2 countries
• Sites: 17

Brief Summary

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

Conditions

Advanced Solid Tumors Cancer; Pancreatic Ductal Adenocarcinoma; RAS Mutation

Keywords

GFH276; PDAC; RAS Mutation; solid tumors

Outcome Measures

Primary Outcomes (10)

• Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events

  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)

  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)

  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

  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

  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

  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

  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

  Number of participants with abnormality in Physical Examination Findings

  up to 24 months

• Phase Ib: Number of participants with abnormality in PR interval

  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)

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

  up to 24 months

Secondary Outcomes (9)

• Phase II: Incidence and Severity of AE and SAE

  From the first dose until 30 days after the last dose, assessed up to 24 months

• 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

  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

  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

  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

Study Arms (3)

Arm A: GFH276 + Cetuximab

EXPERIMENTAL

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

Drug: GFH276; Drug: Cetuximab

Arm B: GFH276 + AG

EXPERIMENTAL

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

Drug: GFH276; Drug: Nab paclitaxel; Drug: Gemcitabine

Arm C: GFH276 + mFOLFIRINOX

EXPERIMENTAL

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.

Drug: GFH276; Drug: Fluorouracil; Drug: Leucovorin; Drug: Irinotecan; Drug: Oxaliplatin

Interventions

GFH276 DRUG

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

Arm A: GFH276 + Cetuximab; Arm B: GFH276 + AG; Arm C: GFH276 + mFOLFIRINOX

Cetuximab DRUG

Intravenous cetuximab at a dose of 500 mg/m²

Arm A: GFH276 + Cetuximab

Nab paclitaxel DRUG

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

Arm B: GFH276 + AG

Gemcitabine DRUG

Intravenous Gemcitabine at a dose of 1000 mg/m².

Arm B: GFH276 + AG

Fluorouracil DRUG

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

Arm C: GFH276 + mFOLFIRINOX

Leucovorin DRUG

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

Arm C: GFH276 + mFOLFIRINOX

Irinotecan DRUG

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

Arm C: GFH276 + mFOLFIRINOX

Oxaliplatin DRUG

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

Arm C: GFH276 + mFOLFIRINOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Genfleet Therapeutics (Shanghai) Inc.: lead

Study Sites (17)

Concord Cancer Centre, Concord Repatriation General Hospital, Sydney Local Health District

Concord, New South Wales, 2139, Australia

Location

Macquarie University / Clinical Trials Unit

North Ryde, New South Wales, 2109, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Monash Health (Monash Medical Centre)

Clayton, Victoria, 3168, Australia

Location

Northern Health

Epping, Victoria, 3076, Australia

Location

PASO Medical

Frankston, Victoria, 3199, Australia

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

Location

The Third Affiliated Hospital (Cancer Hospital) of Harbin Medical University

Harbin, Heilongjiang, 150081, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

The First Affiliated Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Shandong First Medical University Affiliated Tumor Hospital

Jinan, Shandong, 250117, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

MeSH Terms

Interventions

Cetuximab; Taxes; Gemcitabine; Fluorouracil; Leucovorin; Irinotecan; Oxaliplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Uracil; Pyrimidinones; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

Central Study Contacts

Bai Li

CONTACT

18201333260; lbai@genfleet.com

Zhang Pingping

CONTACT

18758558734; ppzhang@genfleet.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: July 1, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (11); AU (6)