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