Clinical trial NCT02055066: A Phase 1b Study of ARGX-111 in Patients With Advanced Cancer.
Official title: A Phase 1b Study of ARGX-111 in Patients With Advanced Cancer Over-expressing the c-Met Protein.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: cancer
c-MET
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2014-02-04
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity
timeFrame: 1 month
Secondary outcomes:
measure: Pharmacokinetic profiles (Cmax , Ctrough, AUC, Vd , clearance, and half-life)
timeFrame: C1 D1 (pre, 0h, 2h, 6h, 12h, 24h), C1D8, C1D15; Cycle ≥2 o D1 pre-/post-dose
measure: Biomarkers (Hepatocyte growth factor; ADCC)
timeFrame: Base-line and pre-dose at each cycle for an average of 4 months
measure: Incidence of adverse events per dose level
timeFrame: for an average of 4 months
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Universitair Zieckenhuis Antwerpen
city: Brussels
country: Belgium
facility: Institut Jules Bordet
Study officials:
affiliation: Jules Bordet Institute
name: Ahmad Awada, MD
role: PRINCIPAL_INVESTIGATOR
References: