E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-line treatment of advanced High Grade Serous Ovarian Cancer |
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E.1.1.1 | Medical condition in easily understood language |
High Grade Serous Ovarian Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. Among patients with detectable ctDNA at baseline, to evaluate whether the reduction from baseline in circulating tumor DNA at Cycle 3 (ΔctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) therapy than in those receiving pembrolizumab + SOC therapy |
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E.2.2 | Secondary objectives of the trial |
1. Among patients with detectable ctDNA at baseline, to evaluate the association between neoadjuvant ΔctDNA 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <25, then a workup should be negative for the presence of a non-OC tumor (eg, breast or GI cancers including CRC) 5. Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion 6. Is female and at least 18 years of age on the day of providing documented informed consent 7. Has an ECOG PS of 0 or 1, as assessed within 7 days prior to the first dose of study intervention on Day 1 of Cycle 1 8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and: - Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: ◦ MK-4830: 180 days ◦ Pembrolizumab: 120 days ◦ Chemotherapy: 180 days ◦ Avastin (or biosimilar if administered): 180 days The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed - Has a negative highly sensitive pregnancy test within either 24 hours (urine) or 72 hours (serum) before the first dose of study intervention. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive - Has had her medical history, menstrual history, and recent sexual activity reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy 9.The participant (or legally acceptable representative) has provided documented informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the study without participating in FBR 10. Has an adequate organ function; all screening laboratory tests should be performed within 7 days prior to the first dose of study intervention on Day 1 of Cycle 1 |
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E.4 | Principal 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 it is not in the best interest of the participant to participate, in the opinion of the treating investigator 20. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study 21. Has current, clinically relevant bowel obstruction (including subocclusive disease), abdominal fistula, or Gl perforation, related to underlying epithelial OC 22. Has a history of hemorrhage, hemoptysis, or active GI bleeding within 6 months prior to randomization 23. Has uncontrolled hypertension 24. Has had an allogenic tissue/solid organ transplant 25. Has either had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery 26. In the judgment of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Chile |
Israel |
Korea, Republic of |
Singapore |
United States |
France |
Poland |
Spain |
Italy |
Belgium |
Russian Federation |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 29 |