Cancer
Conditions
Keywords
cancer, c-MET
Brief summary
This a first-in-human study of an antibody blocking the function of the oncogene c-met in patients with cancer.
Detailed description
This Phase 1b trial will characterize the safety profile of ARGX 111 and will thus provide the first elements towards establishing an accurate risk-benefit assessment for ARGX 111 in cancer patients.
Interventions
DRUGARGX-111
Sponsors
argenx
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. Written informed consent. 2. Age ≥ 18 years. 3. Performance status of 0 or 1. 4. Histological diagnosis of malignancy. 5. Cancer relapsing after, or refractory to standard therapy. 6. Malignancy over-expressing the c Met protein. 7. Presence of circulating tumor cells (CTCs). 8. At least one tumor lesion \> 2 cm on PET/CT. 9. Serum albumin \> 35 g/L. 10. Absolute neutrophil count (ANC) \> 1.0 x 109/L. 11. Hemoglobin \> 90 g/L (0.9 g/dL). 12. Platelet count ≥ 75 x 109/L. 13. Coagulation parameters ≤ 1.5 x ULN. 14. Total bilirubin ≤ 1.5 x upper limit of normal (ULN). 15. Creatine Phosphokinase (CPK) ≤ 2.5 x ULN. 16. Serum creatinine ≤ 1.5 x ULN. 17. Ability to comply with protocol-specified procedures/evaluations and scheduled visits.
Exclusion criteria
1. History or clinical evidence of neoplastic central nervous system (CNS) involvement. 2. Major surgery within 4 weeks of ARGX 111 first dose administration. 3. Systemic glucocorticoid administration at doses greater than physiological replacement (prednisone 20 mg equivalent) within 3 weeks of ARGX 111 first dose administration. 4. Cytotoxic chemotherapy within 3 weeks of ARGX 111 first dose administration. 5. Radiation therapy with curative intent within 3 weeks of ARGX 111 first dose administration. 6. Biological therapy (monoclonal antibodies) within 4 weeks of ARGX 111 first dose administration. 7. Biological therapy (other than monoclonal antibodies) within 5 half-lives of ARGX 111 first dose administration. 8. Unresolved Grade 3 or 4 toxicity from prior therapy, including experimental therapy. 9. History of recurrent Grade 3 or 4 toxicity from anti c Met therapy. 10. Uncontrolled diabetes, defined as fasting glycemia \> 150 mg/dl). 11. Active, untreated viral, bacterial, or systemic fungal infection. 12. Any clinical finding, including psychiatric and behavioral problems, which, in the opinion of the Investigator, precludes the patient from safely participating in the study. 13. Childbearing potential (unless using an adequate measure of contraception). 14. Pregnancy or lactation. 15. History of severe (Grade 3 or 4) hypersensitivity to recombinant proteins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity | 1 month | Number of patients with grade 3 or 4 toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profiles (Cmax , Ctrough, AUC, Vd , clearance, and half-life) | C1 D1 (pre, 0h, 2h, 6h, 12h, 24h), C1D8, C1D15; Cycle ≥2 o D1 pre-/post-dose | Measurement of drug concentration in the blood |
| Biomarkers (Hepatocyte growth factor; ADCC) | Base-line and pre-dose at each cycle for an average of 4 months | measurements of cytokine changes in blood as a result of drug administration |
| Incidence of adverse events per dose level | for an average of 4 months | — |
Countries
Belgium
Outcome results
None listed