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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma; Advanced Solid Tumors Cancer; RAS Mutation
• Intervention / Treatment: Drug: GFH276; Drug: Cetuximab; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Fluorouracil; Drug: Leucovorin; Drug: Irinotecan; Drug: Oxaliplatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 222
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bai Li; Phone Number: 18201333260; Email: lbai@genfleet.com
• Study Contact Backup: Name: Zhang Pingping; Phone Number: 18758558734; Email: ppzhang@genfleet.com

Study Locations

• Australia
  • New South Wales
    • North Ryde, New South Wales, Australia, 2109
      • Macquarie University / Clinical Trials Unit
      • Contact: PhD
      • Contact: Andrew Parsonson, PhD
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health (Monash Medical Centre)
• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Xianjun Yu, MD; Phone Number: 13801669875; Email: yuxianjun@fudanpci.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: GFH276 + Cetuximab; GFH276 once daily; cetuximab 500 mg/m² intravenous infusion every 2 weeks.	Drug: GFH276; Oral GFH276 administered once daily in combination with other study drugs.; Drug: Cetuximab; Intravenous cetuximab at a dose of 500 mg/m²
Experimental: 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	Drug: GFH276; Oral GFH276 administered once daily in combination with other study drugs.; Drug: Nab paclitaxel; Intravenous nab-paclitaxel at a dose of 125 mg/m².; Drug: Gemcitabine; Intravenous Gemcitabine at a dose of 1000 mg/m².
Experimental: 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.	Drug: GFH276; Oral GFH276 administered once daily in combination with other study drugs.; Drug: Fluorouracil; Intravenous Fluorouracil at a dose of 2400 mg/m² via 46-hour infusion.Dosing may follow the above regimen or local institutional standards.; Drug: Leucovorin; Intravenous leucovorin at a dose of 400 mg/m².Dosing may follow the above regimen or local institutional standards.; Drug: Irinotecan; Intravenous irinotecan at a dose of 150 mg/m².Dosing may follow the above regimen or local institutional standards.; Drug: Oxaliplatin; Intravenous oxaliplatin at a dose of 85 mg/m².Dosing may follow the above regimen or local institutional standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	From the first dose until date of death from any cause, assessed up to 24 months
Phase II: Incidence and Severity of AE and SAE	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	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	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	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	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
Time to peak plasma concentration（Tmax） of GFH276	Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Tmax were evaluated.	up to 6 months
Maximum plasma concentration of GFH276	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	Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including AUC0-24 were evaluated.	up to 6 months

Collaborators and Investigators

• Sponsor: Genfleet Therapeutics (Shanghai) Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: solid tumors; PDAC; RAS Mutation; GFH276
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Health Care Economics and Organizations; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Economics; Oxaliplatin; Irinotecan; Cetuximab; Gemcitabine; Fluorouracil; Leucovorin; Taxes
• Other Study ID Numbers: GFH276X0201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No