A Prospective, Open-label, Phase 4 Study to Evaluate the Safety of Pembrolizumab (KEYTRUDA®) in Combination With Indication-specific Chemotherapy or Chemoradiotherapy in Participants Across Multiple Indications in India (KEYNOTE-G44)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 150
- 主要终点
- Number of Participants Who Experienced One or More Adverse Events (AEs)
研究概览
简要总结
The goal of this study is to assess the safety of pembrolizumab with chemotherapy or chemoradiotherapy in participants in India for:
- Advanced gastric or gastroesophageal junction [GEJ] cancer that is (human epidermal growth factor receptor 2 [HER2]-negative and has a programmed death-ligand 1 [PD-L1] combined positive score [CPS] ≥1
- Advanced and/or unresectable biliary tract cancer [BTC], and
- High-risk, locally advanced cervical cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- All
- 接受健康志愿者
- 否
入选标准
- •The participant must have a histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, with locally confirmed programmed death-ligand 1 (PD-L1) CPS ≥
- •Has locally confirmed human epidermal growth factor receptor 2 (HER2) negative cancer.
- •- Has a histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (BTC) (intra or extrahepatic cholangiocarcinoma or gallbladder cancer).
- •Has high-risk locally advanced cervical cancer.
- •Has histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
- •All Cohorts:
- •If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load and has received HBV antiviral therapy for at least 4 weeks and will continue it.
- •If history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
排除标准
- •Has squamous cell or undifferentiated gastric cancer.
- •Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to first dose of study.
- •Had active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks or tumor bleeding within 2 weeks prior to the first dose of study intervention.
- •Has ampullary cancer.
- •Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and/or mucinous cystic neoplasms.
- •Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) BTC (intra or extrahepatic cholangiocarcinoma or gallbladder cancer), with the exception of neoadjuvant/adjuvant therapy, which is allowed.
- •Has known active CNS metastases and/or carcinomatous meningitis.
- •Had active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks or tumor bleeding within 2 weeks prior to the first dose of study intervention.
- •- Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy.
- •All Cohorts:
- •Has hypokalemia.
- •Has hypomagnesemia.
- •Has hypocalcemia.
- •Received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1, or anti-programmed death-ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
- •Has active autoimmune disease that has required systemic treatment in the past 2 years.
- •Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
- •Has a known additional invasive malignancy that is progressing or has required active treatment within the past 3 years.
- •Has history of human immunodeficiency virus (HIV) infection.
- •Has known active tuberculosis.
- •Has not adequately recovered from major surgery or is having ongoing surgical complications.
研究组 & 干预措施
Cohort 3 (Cervical)
Participants with high-risk locally advanced cervical cancer will receive 200 mg pembrolizumab IV Q3W for a maximum of 35 cycles plus 40 mg/m^2 of cisplatin IV weekly for up to 5 infusions concurrent with radiotherapy (RT) and external beam RT and brachytherapy (BT). A cycle is 21 days.
干预措施: External Beam Radiotherapy (Radiation)
Cohort 3 (Cervical)
Participants with high-risk locally advanced cervical cancer will receive 200 mg pembrolizumab IV Q3W for a maximum of 35 cycles plus 40 mg/m^2 of cisplatin IV weekly for up to 5 infusions concurrent with radiotherapy (RT) and external beam RT and brachytherapy (BT). A cycle is 21 days.
干预措施: Brachytherapy (Radiation)
Cohort 1 (Gastric)
Participants with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 will receive 200 mg of pembrolizumab intravenously (IV) every 3 weeks (Q3W) for maximum of 35 cycles plus either 800mg/m^2/day of 5-fluorouracil (5-FU) IV on Days 1 through 5, Q3W and 80mg/m^2 of cisplatin IV on Day 1, Q3W OR 1000mg/m^2 of capecitabine orally twice daily on Days 1 through 14, Q3W and 130mg/m^2 oxaliplatin IV on Day 1, Q3W. A cycle is 21 days.
干预措施: Capecitabine (Drug)
Cohort 1 (Gastric)
Participants with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 will receive 200 mg of pembrolizumab intravenously (IV) every 3 weeks (Q3W) for maximum of 35 cycles plus either 800mg/m^2/day of 5-fluorouracil (5-FU) IV on Days 1 through 5, Q3W and 80mg/m^2 of cisplatin IV on Day 1, Q3W OR 1000mg/m^2 of capecitabine orally twice daily on Days 1 through 14, Q3W and 130mg/m^2 oxaliplatin IV on Day 1, Q3W. A cycle is 21 days.
干预措施: Pembrolizumab (Biological)
Cohort 1 (Gastric)
Participants with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 will receive 200 mg of pembrolizumab intravenously (IV) every 3 weeks (Q3W) for maximum of 35 cycles plus either 800mg/m^2/day of 5-fluorouracil (5-FU) IV on Days 1 through 5, Q3W and 80mg/m^2 of cisplatin IV on Day 1, Q3W OR 1000mg/m^2 of capecitabine orally twice daily on Days 1 through 14, Q3W and 130mg/m^2 oxaliplatin IV on Day 1, Q3W. A cycle is 21 days.
干预措施: 5-Fluorouracil (Drug)
Cohort 1 (Gastric)
Participants with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 will receive 200 mg of pembrolizumab intravenously (IV) every 3 weeks (Q3W) for maximum of 35 cycles plus either 800mg/m^2/day of 5-fluorouracil (5-FU) IV on Days 1 through 5, Q3W and 80mg/m^2 of cisplatin IV on Day 1, Q3W OR 1000mg/m^2 of capecitabine orally twice daily on Days 1 through 14, Q3W and 130mg/m^2 oxaliplatin IV on Day 1, Q3W. A cycle is 21 days.
干预措施: Oxaliplatin (Drug)
Cohort 1 (Gastric)
Participants with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 will receive 200 mg of pembrolizumab intravenously (IV) every 3 weeks (Q3W) for maximum of 35 cycles plus either 800mg/m^2/day of 5-fluorouracil (5-FU) IV on Days 1 through 5, Q3W and 80mg/m^2 of cisplatin IV on Day 1, Q3W OR 1000mg/m^2 of capecitabine orally twice daily on Days 1 through 14, Q3W and 130mg/m^2 oxaliplatin IV on Day 1, Q3W. A cycle is 21 days.
干预措施: Cisplatin (Drug)
Cohort 2 (Biliary)
Participants with advanced/unresectable biliary tract cancer (BTC) will receive 200 mg pembrolizumab IV Q3W for a maximum of 35 cycles plus 1000 mg/m^2 of gemcitabine IV on Days 1 and 8, Q3W and 25 mg/m^2 of cisplatin IV on Days 1 and 8, Q3W for a maximum of 8 cycles. A cycle is 21 days.
干预措施: Pembrolizumab (Biological)
Cohort 2 (Biliary)
Participants with advanced/unresectable biliary tract cancer (BTC) will receive 200 mg pembrolizumab IV Q3W for a maximum of 35 cycles plus 1000 mg/m^2 of gemcitabine IV on Days 1 and 8, Q3W and 25 mg/m^2 of cisplatin IV on Days 1 and 8, Q3W for a maximum of 8 cycles. A cycle is 21 days.
干预措施: Cisplatin (Drug)
Cohort 3 (Cervical)
Participants with high-risk locally advanced cervical cancer will receive 200 mg pembrolizumab IV Q3W for a maximum of 35 cycles plus 40 mg/m^2 of cisplatin IV weekly for up to 5 infusions concurrent with radiotherapy (RT) and external beam RT and brachytherapy (BT). A cycle is 21 days.
干预措施: Pembrolizumab (Biological)
Cohort 2 (Biliary)
Participants with advanced/unresectable biliary tract cancer (BTC) will receive 200 mg pembrolizumab IV Q3W for a maximum of 35 cycles plus 1000 mg/m^2 of gemcitabine IV on Days 1 and 8, Q3W and 25 mg/m^2 of cisplatin IV on Days 1 and 8, Q3W for a maximum of 8 cycles. A cycle is 21 days.
干预措施: Gemcitabine (Drug)
Cohort 3 (Cervical)
Participants with high-risk locally advanced cervical cancer will receive 200 mg pembrolizumab IV Q3W for a maximum of 35 cycles plus 40 mg/m^2 of cisplatin IV weekly for up to 5 infusions concurrent with radiotherapy (RT) and external beam RT and brachytherapy (BT). A cycle is 21 days.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Number of Participants Who Experienced One or More Adverse Events (AEs)
时间窗: Up to approximately 27 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.
Number of Participants Who Discontinued Study Intervention Due to an AE
时间窗: Up to approximately 24 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study intervention due to AEs will be reported.
次要结局
未报告次要终点