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

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

Detailed Description
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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.

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

Conditions
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Cancer

Intervention / Treatment
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* Drug: ARGX-111


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Age ≥ 18 years. Performance status of 0 or 1. Histological diagnosis of malignancy. Cancer relapsing after, or refractory to standard therapy. Malignancy over-expressing the c Met protein. Presence of circulating tumor cells (CTCs). At least one tumor lesion > 2 cm on PET/CT. Serum albumin > 35 g/L. Absolute neutrophil count (ANC) > 1.0 x 109/L. Hemoglobin > 90 g/L (0.9 g/dL). Platelet count ≥ 75 x 109/L. Coagulation parameters ≤ 1.5 x ULN. Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Creatine Phosphokinase (CPK) ≤ 2.5 x ULN. Serum creatinine ≤ 1.5 x ULN. Ability to comply with protocol-specified procedures/evaluations and scheduled visits. Exclusion Criteria: History or clinical evidence of neoplastic central nervous system (CNS) involvement. Major surgery within 4 weeks of ARGX 111 first dose administration. Systemic glucocorticoid administration at doses greater than physiological replacement (prednisone 20 mg equivalent) within 3 weeks of ARGX 111 first dose administration. Cytotoxic chemotherapy within 3 weeks of ARGX 111 first dose administration. Radiation therapy with curative intent within 3 weeks of ARGX 111 first dose administration. Biological therapy (monoclonal antibodies) within 4 weeks of ARGX 111 first dose administration. Biological therapy (other than monoclonal antibodies) within 5 half-lives of ARGX 111 first dose administration. Unresolved Grade 3 or 4 toxicity from prior therapy, including experimental therapy. History of recurrent Grade 3 or 4 toxicity from anti c Met therapy. Uncontrolled diabetes, defined as fasting glycemia > 150 mg/dl). Active, untreated viral, bacterial, or systemic fungal infection. Any clinical finding, including psychiatric and behavioral problems, which, in the opinion of the Investigator, precludes the patient from safely participating in the study. Childbearing potential (unless using an adequate measure of contraception). Pregnancy or lactation. History of severe (Grade 3 or 4) hypersensitivity to recombinant proteins.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, c-MET