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

A Phase 1b Study of ARGX-111 in Patients With Advanced Cancer Over-expressing the c-Met Protein.

This a first-in-human study of an antibody blocking the function of the oncogene c-met in patients with cancer.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: ARGX-111

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • Universitair Zieckenhuis Antwerpen
  • Brussels, Belgium
    • Institut Jules Bordet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; ARGX-111 0.3 mg/kg	Drug: ARGX-111
Experimental: Arm 2; ARGX-111 1.0 mg/kg	Drug: ARGX-111
Experimental: Arm 3; ARGX-111 3.0 mg/kg	Drug: ARGX-111
Experimental: Arm 4; ARGX-111 10 mg/kg	Drug: ARGX-111

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity	Number of patients with grade 3 or 4 toxicity	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profiles (Cmax , Ctrough, AUC, Vd , clearance, and half-life)	Measurement of drug concentration in the blood	C1 D1 (pre, 0h, 2h, 6h, 12h, 24h), C1D8, C1D15; Cycle ≥2 o D1 pre-/post-dose
Biomarkers (Hepatocyte growth factor; ADCC)	measurements of cytokine changes in blood as a result of drug administration	Base-line and pre-dose at each cycle for an average of 4 months
Incidence of adverse events per dose level		for an average of 4 months

Collaborators and Investigators

• Sponsor: argenx
• Investigators: Principal Investigator: Ahmad Awada, MD, Jules Bordet Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: January 31, 2014
• First Submitted That Met QC Criteria: February 3, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Actual): April 21, 2017
• Last Update Submitted That Met QC Criteria: April 20, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: cancer; c-MET
• Other Study ID Numbers: ARGX-111-1301