A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Paclitaxel With or Without Bevacizumab for the Treatment of Platinum-resistant Recurrent Ovarian Cancer (KEYNOTE-B96/ENGOT-ov65)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 643
- 试验地点
- 187
- 主要终点
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Positive Tumors (Combined Positive Score [CPS] ≥1)
研究概览
简要总结
The primary objective is to compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator. The hypotheses are that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for participants with programmed cell death ligand 1 (PD-L1) positive tumors (Combined Positive Score [CPS] ≥1) and that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for all participants.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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 epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
- •Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-programmed cell death 1 protein (PD-1)/anti-programmed cell death ligand 1 (PD-L1) therapy, bevacizumab, or hormonal therapy; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
- •Has provided documented informed consent for the study.
- •Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
- •Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
- •For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of <1% per year).
- •Has radiographically evaluable disease, either measurable or nonmeasurable per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by the local site investigator.
- •Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
- •Have adequate organ function.
排除标准
- •Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.
- •Has primary platinum-refractory disease, defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of first-line platinum-based therapy.
- •Has prior disease progression on weekly paclitaxel alone.
- •Has received >2 prior lines of systemic therapy for OC.
- •Has received prior systemic anticancer therapy including investigational agents or maintenance therapy (including bevacizumab maintenance therapy), within 4 weeks before randomization.
- •Has received prior radiation therapy within 2 weeks of start of study intervention.
- •Has not recovered adequately from surgery and/or any complications from the surgery.
- •Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant erythropoietin) within 4 weeks before randomization.
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- •Has received investigational agent or has used an investigational device within 4 weeks prior to study intervention.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •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 a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study.
- •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- •Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
- •Has had an allogenic tissue/solid organ transplant.
- •For bevacizumab treatment
- •Has uncontrolled hypertension.
- •Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
- •Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.
研究组 & 干预措施
Pembrolizumab + paclitaxel ± bevacizumab
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + paclitaxel ± bevacizumab
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Paclitaxel (Drug)
Pembrolizumab + paclitaxel ± bevacizumab
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Bevacizumab (Drug)
Pembrolizumab + paclitaxel ± bevacizumab
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Docetaxel (Drug)
Placebo + paclitaxel ± bevacizumab
Participants receive placebo via IV infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Paclitaxel (Drug)
Placebo + paclitaxel ± bevacizumab
Participants receive placebo via IV infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Bevacizumab (Drug)
Placebo + paclitaxel ± bevacizumab
Participants receive placebo via IV infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Placebo for pembrolizumab (Other)
Placebo + paclitaxel ± bevacizumab
Participants receive placebo via IV infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Positive Tumors (Combined Positive Score [CPS] ≥1)
时间窗: Up to ~38 months
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). The appearance of one or more lesions and the unequivocal progression of non-target lesions was also considered PD. Per protocol, PFS per RECIST 1.1 as assessed by the Investigator in participants with PD-L1 CPS ≥1 is reported here. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data.
PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants
时间窗: Up to ~38 months
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). The appearance of one or more lesions and the unequivocal progression of non-target lesions was also considered PD. PFS per RECIST 1.1 as assessed by the Investigator will be reported for all participants. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data.
次要结局
- Overall Survival (OS)(Up to ~64 months)
- Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline and up to ~64 months)
- Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30(Up to ~64 months)
- Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale(Baseline and up to ~64 months)
- TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale(Up to ~64 months)
- PFS Per RECIST 1.1 by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1(Up to ~38 months)
- PFS Per RECIST 1.1 by Blinded Independent Central Review (BICR) in All Participants(Up to ~38 months)
- Number of Participants Who Experience an Adverse Event (AE)(Up to ~64 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to ~64 months)