PankoMab-GEX™ Versus Placebo as Maintenance Therapy in Advanced Ovarian Cancer
PankoMab-GEX™ Versus Placebo as Maintenance Therapy in Advanced Ovarian Cancer
Efficacy of PankoMab-GEX vs Placebo in maintaining a response to chemotherapy in advanced
 ovarian, fallopian tube or primary peritoneal cancer.
The study is to evaluate the efficacy of PankoMab-GEX vs Placebo in maintaining response
 after 2nd to 5th line of chemotherapy in patients with epithelial ovarian or fallopian tube
 or primary peritoneal cancer. Patients must have responded to platinum based chemotherapy in
 a previous line, while the response to the most recent Pt-based chemotherapy must not have
 lasted more than 12 months. In addition the response between most recent 2 lines of
 chemotherapy prior start of study medication must not have lasted more than 12 months.
Inclusion Criteria:

 1. Female patients ≥18 years of age

 2. Histologically-confirmed, TA-MUC1-positive, recurrent epithelial ovarian, or
 fallopian-tube cancer or primary peritoneal cancer with high-grade (Grade 2 or 3)
 serous features or a serous component

 3. Availability of tumor tissue samples (slices or block) for immune-histological
 confirmation of TA-MUC1 status (tissue samples could also be stored for other further
 specified biomarker assessments)

 4. Patients were to have received at least 2 lines but not more than 5 lines of
 chemotherapy prior to start of maintenance treatment; neo-adjuvant lines did not count
 as previous lines of treatment

 5. Patients had to have a documented response to or SD following the most recent line of
 chemotherapy (any regimen and duration in accordance with local or international
 guidelines or within IEC-approved studies) and received the last dose of said
 chemotherapy ≤6 weeks prior to randomization (response to prior chemotherapy was
 defined as a PR/CR according to radiological response criteria and/or a confirmed
 decline in tumor marker CA125 ≥50% from the pre-treatment value for patients who had a
 pre-treatment value ≥2 x the upper limit of normal [ULN]; SD was defined as stable
 disease according to radiological response criteria with a confirmed lack of increase
 in tumor marker CA125 from the pre-treatment value for patients who had a
 pre-treatment value ≥2 × ULN and no clinical progression). Prior to randomization,
 CA125 had to be below the ULN, or CA125 levels were not to increase >15% within a time
 frame >7 days if above the ULN

 6. Progression-free interval of ≤12 months immediately preceding the chemotherapy to
 which the patient had just responded

 7. Sensitive or resistant to the most recent platinum-based chemotherapy preceding the
 chemotherapy to which the patient had just responded (sensitivity was thereby defined
 as a recurrence of disease >6 to ≤12 months after the end of platinum-based
 chemotherapy, and resistantance was defined as a recurrence of disease ≤6 months after
 the end of the platinum-based chemotherapy)

 8. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

 9. Recovered from all chemotherapy-related toxicities to Grade 1 or Grade 0 according to
 the NCI-CTCAE Version 4.0, with the exception of alopecia (any grade) and peripheral
 neuropathy (≤Grade 2)

 10. Adequate bone marrow and hepatic function at Screening:

 -  Hemoglobin ≥9 g/dL

 -  White blood cell count ≥3.0 × 109/L

 -  Absolute neutrophil count ≥1.5 × 109/L- Platelet count ≥100 × 109/L

 -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × ULN (<5
 × ULN in case of liver metastases)

 -  Bilirubin <1.5 × ULN (<3 × ULN in case of liver metastases)

 -  Creatinine <1.5 × ULN

 11. Any patient with childbearing potential (i.e. not surgically sterile or
 post-menopausal for >1 year) had to use highly effective contraceptives with a Pearl
 index <1% according to the "Note for guidance on non-clinical safety studies for the
 conduct of human clinical trials and marketing authorization for pharmaceuticals"
 (CPMP/ICH/286/95) of the European Medicines Agency (EMA). (Although pregnancy was
 unlikely to occur in this patient population, any patient with childbearing potential
 had to be withdrawn from the study in the event of pregnancy)

 12. Life expectancy >3 months

 13. Ability and willingness to give written informed consent

 Exclusion criteria:

 1. Refractory to platinum-based chemotherapy (defined as remained progressive or became
 progressive under any previous platinum-based regimen)

 2. Progression-free interval of >12 months after the most recent antecedent
 platinum-based chemotherapy regimen

 3. Concomitant anti-tumor therapy or immunotherapy

 4. Treatment with monoclonal antibodies or investigational agents ≤30 days before
 randomization (prior anti-MUC1 therapy was not permitted at any time)

 5. Limited-field radiotherapy ≤30 days before randomization (extensive prior radiotherapy
 during or following the last line of chemotherapy was not permitted; radiotherapy
 prior to the last line of chemotherapy was permitted)

 6. Prior allergic reaction to a monoclonal antibody, Grade 3 IRR or any Grade 4 reaction
 to a monoclonal antibody

 7. Known sensitivity to any component of the test product

 8. Contraindication to the pre-medication used in this study (paracetamol/acetaminophen,
 H1 and/or H2 receptor antagonists, or steroids)

 9. Clinical evidence of brain metastasis or leptomeningeal involvement

 10. Patients with second primary cancer, except adequately treated non-melanoma skin
 cancer, curatively treated in-situ cancer of the cervix, ductal carcinoma in situ,
 Stage 1 Grade 1 endometrial carcinoma, or other solid tumors including lymphomas
 (without bone marrow involvement) curatively treated with no evidence of disease for
 ≥5 years

 11. Primary or secondary immune deficiency

 12. Clinically active infections >Grade 2 using NCI-CTCAE version 4.0

 13. Active hepatitis B or C or infection with human immunodeficiency virus (HIV)

 14. Myocardial infarction within 6 months prior to Screening

 15. Symptomatic congestive heart failure (New York Heart Association Grade 3 or 4),
 unstable angina pectoris within 6 months prior to Screening, significant cardiac
 arrhythmia or history of stroke or transient ischemic attack within 1 year prior to
 Screening

 16. Prior or planned major surgery within 30 days prior to randomization and/or incomplete
 recovery from prior surgery

 17. Concomitant use of systemic steroids, except for inhaled, topical or nasal application
 within 30 days prior to randomization (steroids used for pre-medication were
 permitted)

 18. Active drug or alcohol abuse

 19. Any uncontrolled medical condition that could have put the patient at high risk during
 treatment with an investigational drug, including unstable diabetes mellitus, vena
 cava syndrome, or chronic symptomatic respiratory disease

 20. Pregnancy or lactation

 21. Legal incompetence, limited legal competence, or detainment in an institution for
 official or legal reasons

 22. Receipt of any other investigational medicinal product within the last 30 days before
 randomization or any previous PankoMab-GEX™ administration