A Randomized, Double-blind, Adaptive, Phase II/III Study of GSK3359609 or Placebo in Combination With Pembrolizumab for First-Line Treatment of PD-L1 Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 315
- 试验地点
- 1
- 主要终点
- OS in the PD-L1 Expression High (CPS ≥20) Population
研究概览
简要总结
The purpose of study is to evaluate if the addition of GSK3359609 to pembrolizumab as first-line treatment improves the efficacy of pembrolizumab in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma/cancer (HNSCC).This is a randomized, double-blind, adaptive Phase II/III study comparing a combination of GSK3359609 inducible T cell co-stimulatory receptor (ICOS) agonist and pembrolizumab to pembrolizumab plus placebo in participants with programmed death receptor 1-ligand 1 (PD-L1) combined positive score (CPS) >=1 R/M HNSCC.
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
- Double (Participant, Investigator)
盲法说明
This will be a double blind study.
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
- •Capable of giving signed informed consent
- •Male or female, age >=18 years
- •Histological or cytological documentation of Head and Neck Squamous Cell Carcinoma (HNSCC) that is considered incurable by local therapies
- •Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx
- •No prior systemic therapy administered in the recurrent or metastatic setting (except for systemic therapy given as part of multimodal treatment for locally advanced disease)
- •Measurable disease per RECIST version 1.1 guidelines
- •ECOG Performance PS score of 0 or 1
- •Adequate organ function
- •Life expectancy of at least 12 weeks
- •Female participants: must not be pregnant, not breastfeeding, and at least one of the following conditions apply:
- •Not a woman of childbearing potential (WOCBP)
- •A WOCBP who agrees to use a method of birth control from 30 days prior to randomization and for at least 120 days after the last dose of study treatment
- •Male participants with female partners of child-bearing potential: must agree to use a highly effective contraception while receiving study treatment and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
- •Provide tumor tissue from excisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) acquired within 2 years prior to randomization for PD-L1 immunohistochemistry (IHC) testing by central laboratory
- •Have PD-L1 Immunohistochemistry (IHC) CPS 1 status by central laboratory testing
- •Have results from testing of Human Papilloma Virus (HPV) status for oropharyngeal cancer
排除标准
- •Prior therapy with an anti-PD-1/L1/L2 and/or anti-ICOS directed agent
- •Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter
- •Major surgery 28 days prior to randomization
- •Has high risk of bleeding
- •Toxicity related to prior treatment that has not resolved to <=Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be<= Grade 2)
- •Received transfusion of blood products or administration of colony stimulating factors within 14 days prior to randomization
- •Central nervous system (CNS) metastases, with the following exception: Participants with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to randomization
- •Invasive malignancy or history of invasive malignancy other than disease under study within the last 3 years, except as noted below:
- •a. Any other invasive malignancy for which the participant was definitively treated, has been disease-free for 3 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical study
- •Autoimmune disease or syndrome that required systemic treatment within the past 2 years
- •Has a diagnosis of immunodeficiency or is receiving systemic steroids (≥10 mg oral prednisone per day or equivalent) or other immunosuppressive agents within 7 days prior to randomization
- •Receipt of any live vaccine within 30 days prior randomization
- •Prior allogeneic/autologous bone marrow or solid organ transplantation
- •Has current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents
- •Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions
- •Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess
- •Recent history of allergen desensitization therapy within 4 weeks of randomization
- •History or evidence of cardiac abnormalities within the 6 months prior to randomization
- •Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice
- •Active infection requiring systemic therapy
- •Known HIV infection, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C active infection
- •History of severe hypersensitivity to monoclonal antibodies or any ingredient used in the study treatment formulations
- •Known history of active tuberculosis
- •Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator
- •Is currently participating in (unless in follow-up phase and 4 weeks have elapsed from last dose of prior investigational agent), or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to date of randomization
- •Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study
研究组 & 干预措施
Participants receiving feladilimab and pembrolizumab
Participants were administered feladilimab (humanized anti-ICOS immunoglobulin G4 [IgG4] monoclonal antibody [mAb]) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an intravenous (IV) infusion once every three weeks.
干预措施: feladilimab (Drug)
Participants receiving feladilimab and pembrolizumab
Participants were administered feladilimab (humanized anti-ICOS immunoglobulin G4 [IgG4] monoclonal antibody [mAb]) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an intravenous (IV) infusion once every three weeks.
干预措施: Pembrolizumab (Drug)
Participants receiving placebo and pembrolizumab
Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion once every three weeks.
干预措施: Pembrolizumab (Drug)
Participants receiving placebo and pembrolizumab
Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion once every three weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
OS in the PD-L1 Expression High (CPS ≥20) Population
时间窗: Up to approximately 16 months
OS was defined as the time from the date of randomization to the date of death due to any cause. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
时间窗: Up to approximately 16 months
OS was defined as the time from the date of randomization to the date of death due to any cause. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population
时间窗: Up to approximately 16 months
PFS per RECIST version (v)1.1 was defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
次要结局
- PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population(Up to approximately 16 months)
- Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population(12 months)
- ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population(Up to approximately 16 months)
- Number of Participants With AEs by Severity(Up to approximately 43 months)
- Number of Participants With SAEs by Severity(Up to approximately 43 months)
- TTD in Physical Function in the PD-L1 CPS ≥1 Population(Up to approximately 16 months)
- PFS Per RECIST in the PD-L1 CPS ≥20 Population(Up to approximately 16 months)
- PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population(Up to approximately 16 months)
- Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population(12 months)
- Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population(Up to approximately 16 months)
- DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population(Up to approximately 16 months)
- Number of Participants With Adverse Events of Special Interest (AESI)(Up to approximately 43 months)
- Milestone OS Rate at 24 Months in the PD-L1 CPS ≥1 Population(24 months)
- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 43 months)
- TTD in Pain in the PD-L1 CPS ≥20 Population(Up to approximately 16 months)
- Milestone OS Rate at 24 Months in the PD-L1 CPS ≥20 Population(24 months)
- Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population(Up to approximately 16 months)
- Number of Participants With AESI by Severity(Up to approximately 43 months)
- Number of Participants With Dose Modifications(Up to approximately 16 months)
- Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population(Up to approximately 16 months)
- Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population(Up to approximately 16 months)
- DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population(Up to approximately 16 months)
- TTD in Physical Function in the PD-L1 CPS ≥20 Population(Up to approximately 16 months)