Phase 1 Trial of IMAB027 in Patients With Recurrent Advanced Ovarian Cancer (OVAR)

Study Overview
=================
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.

Official Title
-----------------
A First-in-human Dose Escalation and Dose Finding Phase 1 Trial of IMAB027 in Patients With Recurrent Advanced Ovarian Cancer (OVAR)

Conditions
-----------------
Ovarian Cancer

Intervention / Treatment
-----------------
* Drug: IMAB027


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed written informed consent Female patients ≥18 years of age, no upper age limit 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) Performance status ECOG 0-2 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 Availability of a FFPE tumor tissue sample or tumor cell positive paracentesis fluid samples (abdominal or pleural cavity) for the assessment of CLDN6 positivity Life expectancy of >12 weeks 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) Patients of child-bearing potential must have a negative β-HCG urine test within 72 hours before receiving treatment Exclusion Criteria: Patient is pregnant or breast-feeding Prior allergic reaction or intolerance to a monoclonal antibody (humanized or chimeric) Any prior anti-tumor therapy within 14 days prior to the start of IMAB027 treatment Other concurrent anticancer therapies HIV infection in medical history or active Hepatitis B or C infection requiring treatment 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 Other investigational agents or devices concurrently or within 14 days before start of IMAB027 treatment Any hemoptysis or bleeding event that is clinically relevant within 2 weeks of first dose of study drug Clinical symptoms of brain metastases or tumor-associated spinal cord compression Need for continuous, systemic immunosuppressive therapy Any other medical condition that would, in the opinion of the Investigator, limit the patient's ability to complete the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMAB027 administration<br>Monotherapy - different dose Levels. | Drug: IMAB027<br>* 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<br>* Other names: ASP1650;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Safety profile including type, frequency, severity, relationship of adverse events to investigational medicinal product, dose limiting toxicities, maximum tolerated dose | 24 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to assess pharmacokinetics | Cmax, AUC, terminal half-life and related pharmacokinetic parameters of IMAB027 | 24 month | 
| to assess antitumoral activity | Disease control rates (CR, PR, SD), ratio previous/current remission time intervals and overall survival | up to 3 years | 
| to assess immunogenicity | Frequency of anti-IMAB027 antibodies | 24 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced ovarian cancer, CLDN6 positive