Advanced Solid Tumors Cancer, CRC (Colorectal Cancer), PDAC
Conditions
Keywords
solid tumors, KRAS G12D Mutations
Brief summary
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_PRODUCTGFH375
GFH375 once daily (QD) .Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.
Sponsors
Genfleet Therapeutics (Shanghai) Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily participate in the study and sign the informed consent form. 2. 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. 3. Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors, with KRAS G12D mutation. 4. Failed standard systemic treatment, or intolerant to standard treatment, or unsuitable for standard treatment, or no standard treatment available. 5. At least one measurable lesions according to RECIST v1.1 6. 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. 7. Have sufficient organ function.
Exclusion criteria
1. Symptomatic brain metastasis, leptomeningeal metastasis, spinal cord compression, or primary brain tumor. 2. Presence of known coexisting other cancer driver genes. 3. Previous or active history of clinically significant cardiovascular dysfunction. 4. Presence of active infection. 5. History of central nervous system (CNS) diseases. 6. Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment. 7. Newly diagnosed deep vein thrombosis or pulmonary embolism within 3 months before the first administration of the study treatment. 8. Presence of uncontrolled or symptomatic pleural effusion, ascites, or pericardial effusion. 9. 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. 10. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib: Incidence of Dose-Limiting Toxicity (DLT) Events | up to 28 days |
| Phase Ib: Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE) | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | TTR assessed by investigators |
| 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 | DoR assessed by investigators |
| Plasma concentrations of GFH375 | up to 6 months | Plasma concentrations of GFH375 |
| OS | From the first dose until date of death from any cause, assessed up to 24 months | Overall Survival |
| 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 | Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, as Determined by investagors |
| 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 | DCR assessed by investigators |
Countries
China
Contacts
Primary ContactYolanda Zeng
Backup ContactJunnan Dong
Outcome results
None listed