A Study of GFH375 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors Harboring KRAS G12D Mutation

Official title

A Multicenter, Open-Label, Phase Ib/II Clinical Study to Explore the Efficacy, Pharmacokinetics and Safety/Tolerability of GFH375 in Combination With Cetuximab or Chemotherapy in Participants With Advanced Solid Tumors Harboring KRAS G12D Mutation

Overview

This is a Phase Ib/II clinical study aimed at exploring the safety and efficacy of Regimen A (GFH375 in combination with Cetuximab) and Regimen B (GFH375 in combination with AG) in participants with solid tumors.Phase Ib: To evaluate the safety/tolerability and pharmacokinetic (PK) characteristics of GFH375 in combination with cetuximab or AG in participants with solid tumors, and to explore the efficacy of the combination therapy. Phase II: To evaluate the efficacy, safety/tolerability and PK characteristics of the combination therapy, and to explore the correlation between bio-marker and clinical efficacy.

Interventions

• Combination product GFH375
  GFH375 once daily (QD) .Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.
• Combination product GFH375
  GFH375 once daily (QD). Paclitaxel (albumin-bound) at 125 mg/m² and gemcitabine at 1000 mg/m² will be administered via intravenous infusion on Days 1, 8, and 15 of each 4-week cycle.

Primary outcome measures

• Phase Ib: Incidence of Dose-Limiting Toxicity (DLT) Events [Time frame: up to 28 days]
• Phase Ib: Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE) [Time frame: From the first dose until 30 days after the last dose, assessed up to 24 months]
• Phase II: Objective Response Rate (ORR) Evaluated by 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]

Secondary outcome measures (7)

• Plasma concentrations of GFH375 [Time frame: up to 6 months]
• Phase II: Incidence and Severity of AE and SAE [Time frame: From the first dose until 30 days after the last dose, assessed up to 24 months]
• 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]
• TTR [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 [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 [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]
• OS [Time frame: From the first dose until date of death from any cause, assessed up to 24 months]

Eligibility criteria

Inclusion criteria

• Voluntarily participate in the study and sign the informed consent form.
• Participants receiving Regimen A must be ≥ 18 years old when signing the informed consent form, and participants receiving Arm B must be 18 - 75 years old.
• Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors, with KRAS G12D mutation.
• Failed standard systemic treatment, or intolerant to standard treatment, or unsuitable for standard treatment, or no standard treatment available.
• At least one measurable lesions according to RECIST v1.1
• Participants receiving Regimen A must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 - 2; participants receiving Regimen B must have an ECOG PS score of 0 - 1.
• Have sufficient organ function.

Exclusion criteria

• Symptomatic brain metastasis, leptomeningeal metastasis, spinal cord compression, or primary brain tumor.
• Presence of known coexisting other cancer driver genes.
• Previous or active history of clinically significant cardiovascular dysfunction.
• Presence of active infection.
• History of central nervous system (CNS) diseases.
• Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment.
• Newly diagnosed deep vein thrombosis or pulmonary embolism within 3 months before the first administration of the study treatment.
• Presence of uncontrolled or symptomatic pleural effusion, ascites, or pericardial effusion.
• Having received major surgery within 28 days before the start of the study treatment; having experienced major trauma within 14 days before the start of the study treatment; or planning to undergo major surgery during the study period.
• Having received radiotherapy within 4 weeks before the start of the study treatment, or having received palliative radiotherapy for bone metastatic lesions within 2 weeks before the start of the study treatment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Beijing Cancer Hospital — Beijing
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT07259590 · GFH375X1202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗