Ovarian Cancer
Conditions
Keywords
Advanced ovarian cancer, CLDN6 positive
Brief summary
Advanced ovarian cancer is a high medical need indication. Cure is not available to these patients and treatment has palliative intent. A proportion of advanced stage ovarian cancer expresses substantial levels of Claudin 6 (CLDN6), a carcino-embryonic transmembrane protein, which is absent from normal adult human tissue. IMAB027 is a monoclonal antibody that binds to CLDN6. Preclinically IMAB027 was shown to inhibit tumor growth and to kill cancer cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This trial is a first-in-human dose escalation and dose finding Phase 1 trial of IMAB027 in patients with recurrent advanced ovarian cancer to assess the safety and tolerability, the pharmacokinetics, the antitumoral activity and the immunogenicity of IMAB027.
Interventions
DRUGIMAB027
Stage 1 (Intrapatient dose escalation): The starting dose is set to 1 mg/m2, followed by 10 mg/m2, 30 mg/m2 and 100 mg/m2 Stage 2 (Interpatient dose escalation): 4 dose level 100 mg/m2, 300 mg/m2, 600 mg/m2, 1000 mg/m2 Extension period: 4 dose level 100 mg/m2, 300 mg/m2, 600 mg/m2, 1000 mg/m2
Sponsors
Ganymed Pharmaceuticals GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent 2. Female patients ≥18 years of age, no upper age limit 3. Histologically or cytologically confirmed CLDN6+ ovarian cancer of any histology type including primary peritoneal or fallopian tube tumors (histological documentation of the original primary tumor is required via a pathology report) 4. Performance status ECOG 0-2 5. Patients with measurable, non-measurable, or evaluable disease: Evaluable disease: defined as a confirmed CA-125 ≥2 x ULN, Measurable disease (RECIST 1.1): defined as at least one lesion that can be accurately measured in at least one dimension 6. Availability of a FFPE tumor tissue sample or tumor cell positive paracentesis fluid samples (abdominal or pleural cavity) for the assessment of CLDN6 positivity 7. Life expectancy of \>12 weeks 8. Adequate organ function defined as: Adequate hematologic function (ANC ≥1000/μl, platelets ≥100.000/μl, hemoglobin ≥9.0 g/dl (can be post transfusion)); Adequate renal function (serum creatinine ≤1.5 mg/dl \[114.5 μmol/l\] or creatinine clearance rate ≥30 ml/min); Adequate liver function (serum total bilirubin ≤2 x ULN, AST/ALT ≤3 x ULN) 9. Patients of child-bearing potential must have a negative β-HCG urine test within 72 hours before receiving treatment
Exclusion criteria
1. Patient is pregnant or breast-feeding 2. Prior allergic reaction or intolerance to a monoclonal antibody (humanized or chimeric) 3. Any prior anti-tumor therapy within 14 days prior to the start of IMAB027 treatment 4. Other concurrent anticancer therapies 5. HIV infection in medical history or active Hepatitis B or C infection requiring treatment 6. History of any one or more of the following cardiovascular conditions within the past 6 months: Myocardial infarction (T-Wave/Non-T-Wave), Unstable angina pectoris Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA), History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT). Patients with recent DVT who have been or are treated with therapeutic anti-coagulant agents (excluding warfarin) for at least 6 weeks are eligible 7. Other investigational agents or devices concurrently or within 14 days before start of IMAB027 treatment 8. Any hemoptysis or bleeding event that is clinically relevant within 2 weeks of first dose of study drug 9. Clinical symptoms of brain metastases or tumor-associated spinal cord compression 10. Need for continuous, systemic immunosuppressive therapy 11. Any other medical condition that would, in the opinion of the Investigator, limit the patient's ability to complete the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | 24 month | Safety profile including type, frequency, severity, relationship of adverse events to investigational medicinal product, dose limiting toxicities, maximum tolerated dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| to assess pharmacokinetics | 24 month | Cmax, AUC, terminal half-life and related pharmacokinetic parameters of IMAB027 |
| to assess antitumoral activity | up to 3 years | Disease control rates (CR, PR, SD), ratio previous/current remission time intervals and overall survival |
| to assess immunogenicity | 24 month | Frequency of anti-IMAB027 antibodies |
Countries
Belgium, Germany
Outcome results
None listed