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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: IMAB027

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • UZ Brussels
  • Leuven, Belgium, 3000
    • UZ Leuven
• Germany
  • Berlin, Germany, 13353
    • Charité - Universitätsmedizin Berlin
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Universitätsklinikum Heidelberg
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Universitäts-Frauenklinik (UFK) Tübingen
    • Ulm, Baden-Württemberg, Germany, 89075
      • Universitätsklinikum Ulm, Frauenklinik
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Universitatsmedizin Mainz
  • Sachsen
    • Dresden, Sachsen, Germany, 1307
      • Gemeinschaftspraxis Hämatologie-Onkologie
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • UKSH Kiel

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMAB027 administration; Monotherapy - different dose Levels.	Drug: IMAB027; 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; 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

Collaborators and Investigators

• Sponsor: Ganymed Pharmaceuticals GmbH
• Investigators: Study Director: Senior Medical Director, Astellas Pharma Global Development, Inc.

Publications and helpful links

Helpful Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2014
• Primary Completion (Actual): October 28, 2015
• Study Completion (Actual): October 28, 2015

Study Registration Dates

• First Submitted: January 29, 2014
• First Submitted That Met QC Criteria: February 3, 2014
• First Posted (Estimated): February 4, 2014

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Advanced ovarian cancer; CLDN6 positive
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms
• Other Study ID Numbers: GM-IMAB-002-01; 2013-002755-15 (EudraCT Number); 1650-CL-0101 (Other Identifier: Astellas Pharma Global Development, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.