A Randomized, Phase 2 Study of Pembrolizumab And Chemotherapy With or Without MK-4830 as Neoadjuvant Treatment for High-Grade Serous Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 45
- 主要终点
- Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA)
研究概览
简要总结
The primary objective is to evaluate in participants with high-grade serous ovarian cancer (HGSOC), whether the reduction from baseline in circulating tumor deoxyribonucleic acid (ctDNA) 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Has histologically-confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer.
- •Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting.
- •Is a candidate for interval debulking surgery.
- •Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion.
- •Has adequate organ functions.
排除标准
- •Has a non-HGSOC histology.
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Has received prior treatment for any stage of ovarian cancer (OC), including radiation or systemic anticancer therapy.
- •Planned or has been administered intraperitoneal chemotherapy as first-line therapy.
- •Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-immunoglobulin-like transcript 4 (ILT4), or anti-human leukocyte antigen (HLA)-G agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- •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.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has severe hypersensitivity to pembrolizumab, carboplatin, paclitaxel (or docetaxel, if applicable), Avastin or biosimilar (if using) and/or any of their excipients.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has an active infection requiring systemic therapy.
- •Has a known history of human immunodeficiency virus (HIV) infection.
- •Has a known history of hepatitis B or known active hepatitis C virus infection.
- •Has received colony-stimulating factors within 4 weeks prior to receiving study intervention on Day 1 of Cycle
- •Has had surgery <6 months prior to Screening to treat borderline ovarian tumors, early-stage OC, or early-stage fallopian tube cancer.
- •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- •Has current, clinically relevant bowel obstruction.
- •Has a history of hemorrhage, hemoptysis, or active gastrointestinal (GI) bleeding within 6 months prior to randomization.
- •Has uncontrolled hypertension.
- •Has had an allogenic tissue/solid organ transplant.
- •Has either had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery.
研究组 & 干预措施
Pembrolizumab + Standard of Care (SOC) + MK-4830
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin Area Under the Curve (AUC) 5 to 6, and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks [Q3W]) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin AUC 5 to 6, and MK-4830 800 mg (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Standard of Care (SOC) + MK-4830
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin Area Under the Curve (AUC) 5 to 6, and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks [Q3W]) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin AUC 5 to 6, and MK-4830 800 mg (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Paclitaxel (Drug)
Pembrolizumab + Standard of Care (SOC) + MK-4830
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin Area Under the Curve (AUC) 5 to 6, and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks [Q3W]) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin AUC 5 to 6, and MK-4830 800 mg (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Carboplatin (Drug)
Pembrolizumab + Standard of Care (SOC) + MK-4830
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin Area Under the Curve (AUC) 5 to 6, and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks [Q3W]) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin AUC 5 to 6, and MK-4830 800 mg (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Avastin (Biological)
Pembrolizumab + Standard of Care (SOC) + MK-4830
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin Area Under the Curve (AUC) 5 to 6, and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks [Q3W]) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin AUC 5 to 6, and MK-4830 800 mg (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: MK-4830 (Biological)
Pembrolizumab + Standard of Care (SOC) + MK-4830
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin Area Under the Curve (AUC) 5 to 6, and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks [Q3W]) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), carboplatin AUC 5 to 6, and MK-4830 800 mg (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Docetaxel (Drug)
Pembrolizumab + SOC
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + SOC
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Paclitaxel (Drug)
Pembrolizumab + SOC
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Carboplatin (Drug)
Pembrolizumab + SOC
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Avastin (Biological)
Pembrolizumab + SOC
Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2 (or docetaxel 75 mg/m^2), and carboplatin AUC 5 to 6 (with avastin [or biosimilar] at the investigator's discretion and per insitutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA)
时间窗: Baseline and Week 7
Blood samples were collected to determine levels of ctDNA. The fold change in the mean mutant/tumor molecules per mL (MTM/mL) at Cycle 3 from baseline is presented.
次要结局
- Participants With Surgery and Pathological Complete Response (pCR): Change From Baseline in ctDNA(Baseline and Week 12)
- Association of Change From Baseline in ctDNA With pCR(Baseline and Week 12)
- Participants With Surgery and Chemotherapy Response Score (CRS): Change From Baseline in ctDNA(Baseline and Week 12)
- Association of Change From Baseline in ctDNA With CRS3(Baseline and Week 12)
- pCR Rate(Up to approximately 12 weeks)
- CRS3 Rate(Up to approximately 12 weeks)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 26 months)
- Number of Participants Who Discontinued Study Intervention Due to an AE(Up to approximately 28 weeks)