NCT04428333终止3 期
A Randomized, Double-Blind, Adaptive, Phase II/III Study of GSK3359609 in Combination With Pembrolizumab and 5FU-Platinum Chemotherapy Versus Placebo in Combination With Pembrolizumab Plus 5FU-Platinum Chemotherapy for First-Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 117
- 试验地点
- 1
- 主要终点
- OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
研究概览
简要总结
The purpose of this study is to evaluate if the addition of GSK3359609 to pembrolizumab in combination with 5FU-platinum based chemotherapy improves the efficacy of the pembrolizumab combination with 5FU-platinum based chemotherapy in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This randomized, double-blinded, Phase II/III study will compare the combination of GSK3359609 with pembrolizumab and 5FU-platinum chemotherapy to placebo in combination with pembrolizumab and 5FU-platinum chemotherapy in participants with recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx or larynx.
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 is 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
- •HNSCC that was diagnosed as recurrent or metastatic and 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 (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease and no disease progression/recurrence within 6 months of the completion of curatively intended systemic treatment).
- •Measurable disease per RECIST version 1.1 guidelines
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or
- •Adequate organ function.
- •Life expectancy of at least 12 weeks.
- •Female participants: must not be pregnant, not breastfeeding, and be either not a woman of childbearing potential (WOCBP); or be a WOCBP who agrees to use a highly effective 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 periods.
- •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 IHC CPS 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, anti-Inducible T Cell Co-Stimulatory Receptor (ICOS) directed agent.
- •Systemic approved or investigational anticancer therapy within 30 days or 5 half lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the date of randomization. - Has high risk of bleeding (examples include but not limited to tumors encasing or infiltrating a major vessel [i.e. carotid, jugular, bronchial artery] and/or exhibits other high-risk features such as an arteriovenous fistula)
- •Active tumor bleeding - Grade 3 or Grade 4 hypercalcemia.
- •Major surgery less than or equal to (<=) 28 days prior to randomization.
- •Participants must have also fully recovered from any surgery (major or minor) and/or its complications before randomization
- •Toxicity from previous anticancer treatment that includes: a. Grade 3/Grade 4 toxicity considered related to prior immunotherapy and that led to treatment discontinuation and b. 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 with the exception of: a. any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=3 years. b. curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma and/or. c. low-risk early stage prostate cancer defined as: Stage T1c or T2a with a Gleason score <=6 and prostatic-specific antigen less than (<)10 nanograms per milliliter (ng/mL) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization.
- •Autoimmune disease or syndrome that required systemic treatment within the past 2 years.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroids (>10 milligram [mg] oral prednisone 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 which include: a. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third-degree atrioventricular block. b. Cardiomyopathy, myocardial infarction, acute coronary syndromes(including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting. c. Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system. d. Symptomatic pericarditis.
- •Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- •Active infection requiring systemic therapy.
- •Known human immunodeficiency virus (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 to the chemotherapies under investigation including any ingredient used in the formulation.
- •Known history of active tuberculosis.
- •Any serious (>=Grade 3) and/or unstable pre-existing medical condition (aside from malignancy).
- •Any 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 or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the date of randomization.
研究组 & 干预措施
Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy
Experimental
干预措施: Feladilimab (Drug)
Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy
Experimental
干预措施: Pembrolizumab (Drug)
Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy
Experimental
干预措施: Platinum based chemotherapy (Drug)
Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy
Experimental
干预措施: Fluorouracil (5FU) (Drug)
Placebo + Pembrolizumab + 5-FU-platinum chemotherapy
Placebo Comparator
干预措施: Pembrolizumab (Drug)
Placebo + Pembrolizumab + 5-FU-platinum chemotherapy
Placebo Comparator
干预措施: Placebo (Drug)
Placebo + Pembrolizumab + 5-FU-platinum chemotherapy
Placebo Comparator
干预措施: Platinum based chemotherapy (Drug)
Placebo + Pembrolizumab + 5-FU-platinum chemotherapy
Placebo Comparator
干预措施: Fluorouracil (5FU) (Drug)
结局指标
主要结局
OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
时间窗: Up to approximately 7 months
OS was defined as the time from the date of randomization until 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) Version (v)1.1 in mITT Population
时间窗: Up to approximately 7 months
PFS per Response Evaluation Criteria in Solid Tumors (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. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Overall Survival (OS) in mITT Population
时间窗: Up to approximately 7 months
OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
次要结局
- PFS Per RECIST v1.1 in the PD-L1 CPS ≥1 Population(Up to approximately 7 months)
- Milestone OS Rate at 12, 24 and 36 Months in mITT Population(Months 12, 24 and 36)
- Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS ≥1 Population(Months 12, 24 and 36)
- Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population(Up to approximately 7 months)
- ORR Per RECIST v1.1 in PD-L1 CPS ≥1 Population(Up to approximately 7 months)
- Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population(Up to approximately 7 months)
- DCR Per RECIST v1.1 in PD-L1 CPS ≥1 Population(Up to approximately 7 months)
- Duration of Response (DoR) Per RECIST v1.1 in mITT Population(Up to approximately 7 months)
- DoR Per RECIST v1.1 in PD-L1 CPS ≥1 Population(Up to approximately 7 months)
- Number of Participants With Adverse Events (AEs) in Safety Population(Up to approximately 37.2 months)
- Number of Participants With Serious Adverse Events (SAEs) in Safety Population(Up to approximately 37.2 months)
- Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population(Up to approximately 37.2 months)
- Number of Participants With AEs in Programmed Death Ligand-1 (PD-L1) Combined Positive Score (CPS ≥1) Population(Up to approximately 37.2 months)
- Number of Participants With SAEs in PD-L1 CPS ≥1 Population(Up to approximately 37.2 months)
- Number of Participants With AESIs in PD-L1 CPS ≥1 Population(Up to approximately 37.2 months)
- Severity of AEs in Safety Population(Up to approximately 37.2 months)
- Severity of SAEs in Safety Population(Up to approximately 37.2 months)
- Severity of AESIs in Safety Population(Up to approximately 37.2 months)
- Severity of AEs in PD-L1 CPS ≥1 Population(Up to approximately 37.2 months)
- Severity of SAEs in PD-L1 CPS ≥1 Population(Up to approximately 37.2 months)
- Severity of AESI in PD-L1 CPS ≥1 Population(Up to approximately 37.2 months)
- Number of Participants With Dose Modifications in Safety Population(Up to approximately 7 months)
- Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population(Up to approximately 7 months)
- Time to Deterioration (TTD) in Pain in mITT Population(Up to approximately 7 months)
- TTD in Pain in PD-L1 CPS ≥1 Population(Up to approximately 7 months)
- TTD in Physical Function in mITT Population(Up to approximately 7 months)
- TTD in Physical Function in PD-L1 CPS ≥1 Population(Up to approximately 7 months)
研究者
研究点 (1)
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