A Phase 1b Study of ARGX-111 in Patients With Advanced Cancer.

Phase 1

Completed

• Conditions: Cancer
• Interventions: Drug: ARGX-111

• Registration Number: NCT02055066
• Lead Sponsor: argenx

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.

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-01-31
• Study First Submitted QC: 2014-02-03
• Study First Posted: 2014-02-04
• Primary Completion: 2017-03
• Study Completion: 2017-03
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-20
• Last Update Posted: 2017-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 3	ARGX-111	ARGX-111 3.0 mg/kg
Arm 2	ARGX-111	ARGX-111 1.0 mg/kg
Arm 4	ARGX-111	ARGX-111 10 mg/kg
Arm 1	ARGX-111	ARGX-111 0.3 mg/kg

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity	1 month	Number of patients with grade 3 or 4 toxicity

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (2)

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Universitair Zieckenhuis Antwerpen; 🇧🇪 Antwerp, Belgium