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

Phase 2Not Yet RecruitingNCT07678593

Genfleet Therapeutics (Shanghai) Inc.222 enrolled

Overview

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

222

Conditions

Advanced Solid Tumors Cancer Pancreatic Ductal Adenocarcinoma RAS Mutation

Interventions

GFH276DRUG

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

CetuximabDRUG

Intravenous cetuximab at a dose of 500 mg/m²

Nab paclitaxelDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (17)

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

Concord, New South Wales, Australia

Macquarie University / Clinical Trials Unit

Outcomes

Primary Outcomes

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

The incidence of DLT events

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: up to 24 months

Phase Ib: Number of participants with abnormality in blood pressure

Central Contacts

Bai Li

CONTACT

18201333260 lbai@genfleet.com

Zhang Pingping

CONTACT

18758558734 ppzhang@genfleet.com

Data from ClinicalTrials.gov

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Secondary Outcomes

Phase II: Incidence and Severity of AE and SAE

Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0

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

DCR

Disease Control Rate (DCR)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Overall Survival

Time frame: From the first dose until date of death from any cause, 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.

Time frame: up to 6 months

Maximum plasma concentration of GFH276

Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Cmax were evaluated.

Time frame: 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.

Time frame: up to 6 months