First-line treatment of advanced High Grade Serous Ovarian Cancer MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has histologically-confirmed FIGO Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer 2. Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting 3. Is a candidate for interval debulking surgery 4. Has either a CA-125 (kilounits/L):CEA (ng/mL) ratio =25 or, if the CA-125:CEA ratio is =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Has a non-HGSOC histology 2. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease 3 .Has a known additional malignancy that is progressing or has required active treatment within the past 3 years 4. Has received prior treatment for any stage of OC, including radiation or systemic anticancer therapy (eg, chemotherapy, hormonal therapy, immunotherapy, investigational therapy) 5. Is a participant for whom intraperitoneal chemotherapy is planned or has been administered as first-line therapy 6. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-ILT4, or anti-HLA-G agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) or MDSC-directed therapy 7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed 8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (indosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication 10. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks by repeat imaging , clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study intervention 11. Has resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 msec, electrolyte disturbances, etc.), or participant has congenital long QT syndrome 12. Has severe hypersensitivity (=Grade 3) to pembrolizumab, carboplatin, paclitaxel (or docetaxel, if applicable), Avastin or biosimilar (if using) and/or any of their excipients 13. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed 14. Has an active infection, requiring systemic therapy 15. Has a known history of HIV infection 16. Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection 17. Has received colony-stimulating factors (eg, G-CSF, GM-CSF, or recombinant erythropoietin) within 4 weeks (28 days) prior to receiving study intervention on Day 1 of Cycle 1 18. Has had surgery <6 months prior to Screening to treat borderline ovarian tumors, early-stage OC, or early-stage fallopian tube cancer 19. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Among patients with detectable ctDNA at baseline, to evaluate whether the reduction from baseline in circulating tumor DNA at Cycle 3 (?ctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) chemotherapy than in those receiving pembrolizumab + SOC.;Secondary Objective: 1. Among patients with detectable ctDNA at baseline, to evaluate the association between neoadjuvant ?ctDNA at Cycle 3 from baseline and surgical outcomes 2. To estimate the difference in pCR and CRS following neoadjuvant treatment between arms 3. To evaluate the safety and tolerability of MK-4830 administered with pembrolizumab and chemotherapy;Primary end point(s): 1. Change from Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA);Timepoint(s) of evaluation of this end point: 1. Baseline and Week 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from Baseline in Neoadjuvant ctDNA 2. Pathological Complete Response (pCR) Rate 3. Chemotherapy Response Score (CRS) 4. Number of Participants Who Experienced an Adverse Event (AE) 5. Number of Participants Who Discontinued Study Treatment Due to an AE;Timepoint(s) of evaluation of this end point: 1. Baseline and Week 7 2. Up to approximately 12 Weeks 3. Up to approximately 12 Weeks 4. Up to approximately 40 Weeks 5. Up to approximately 28 Weeks | — |
Countries
Belgium, Canada, Chile, France, Israel, Italy, Korea, Republic of, Poland, Russian Federation, Singapore, Spain, United States
Contacts
Public ContactInvestigación clínica
Merck Sharp & Dohme de España SA
Outcome results
None listed