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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04428333




Registration number
NCT04428333
Ethics application status
Date submitted
9/06/2020
Date registered
11/06/2020

Titles & IDs
Public title
Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Scientific title
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
Secondary ID [1] 0 0
2019-003981-42
Secondary ID [2] 0 0
209227
Universal Trial Number (UTN)
Trial acronym
INDUCE-4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Head and Neck 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Feladilimab
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Platinum based chemotherapy
Treatment: Drugs - Fluorouracil (5FU)

Experimental: Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy -

Placebo comparator: Placebo + Pembrolizumab + 5-FU-platinum chemotherapy -


Treatment: Drugs: Feladilimab
Humanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 (IgG4) monoclonal antibody (mAb)

Treatment: Drugs: Pembrolizumab
Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb

Treatment: Drugs: Placebo
Sterile normal saline

Treatment: Drugs: Platinum based chemotherapy
Cisplatin/carboplatin

Treatment: Drugs: Fluorouracil (5FU)
5-fluorouracil

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) in mITT Population
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Up to approximately 7 months
Primary outcome [2] 0 0
OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) =1 Population
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Up to approximately 7 months
Primary outcome [3] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in mITT Population
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Up to approximately 7 months
Secondary outcome [1] 0 0
PFS Per RECIST v1.1 in the PD-L1 CPS =1 Population
Assessment method [1] 0 0
PFS per RECIST v1.1 was defined as the time from the date of randomization until the date of 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.
Timepoint [1] 0 0
Up to approximately 7 months
Secondary outcome [2] 0 0
Milestone OS Rate at 12, 24 and 36 Months in mITT Population
Assessment method [2] 0 0
Milestone OS rate at 12, 24, and 36 months was not evaluated.
Timepoint [2] 0 0
Months 12, 24 and 36
Secondary outcome [3] 0 0
Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS =1 Population
Assessment method [3] 0 0
Milestone OS rate at 12, 24, and 36 months was not evaluated. 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.
Timepoint [3] 0 0
Months 12, 24 and 36
Secondary outcome [4] 0 0
Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population
Assessment method [4] 0 0
ORR per RECIST v1.1 was defined as the proportion of the participants who have a complete response (CR) or partial response (PR) as the best overall response per RECIST v1.1 based upon investigator assessment. As a randomized double-blind study in which primary endpoints are OS and PFS, the confirmation of CR and PR was not required. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted.
Timepoint [4] 0 0
Up to approximately 7 months
Secondary outcome [5] 0 0
ORR Per RECIST v1.1 in PD-L1 CPS =1 Population
Assessment method [5] 0 0
ORR per RECIST v1.1 was defined as the proportion of the participants who have a complete response (CR) or partial response (PR) as the best overall response per RECIST v1.1 based upon investigator assessment. As a randomized double-blind study in which primary endpoints are OS and PFS, the confirmation of CR and PR was not required. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. 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.
Timepoint [5] 0 0
Up to approximately 7 months
Secondary outcome [6] 0 0
Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population
Assessment method [6] 0 0
DCR per RECIST v1.1 based upon investigator assessment, was defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 15 weeks. A status of SD=15 weeks will be assigned if the follow-up disease assessment has met the SD criteria at least once after the date of randomization at a minimum of 14 weeks (98 days) considering a one-week visit window. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted.
Timepoint [6] 0 0
Up to approximately 7 months
Secondary outcome [7] 0 0
DCR Per RECIST v1.1 in PD-L1 CPS =1 Population
Assessment method [7] 0 0
DCR per RECIST v1.1 based upon investigator assessment, was defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 15 weeks. A status of SD=15 weeks will be assigned if the follow-up disease assessment has met the SD criteria at least once after the date of randomization at a minimum of 14 weeks (98 days) considering a one-week visit window. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. 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.
Timepoint [7] 0 0
Up to approximately 7 months
Secondary outcome [8] 0 0
Duration of Response (DoR) Per RECIST v1.1 in mITT Population
Assessment method [8] 0 0
DoR per RECIST v1.1 is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. Kaplan-Meier estimate for the median DoR is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Timepoint [8] 0 0
Up to approximately 7 months
Secondary outcome [9] 0 0
DoR Per RECIST v1.1 in PD-L1 CPS =1 Population
Assessment method [9] 0 0
DoR per RECIST v1.1 is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. Kaplan-Meier estimate for the median DoR is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. 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.
Timepoint [9] 0 0
Up to approximately 7 months
Secondary outcome [10] 0 0
Number of Participants With Adverse Events (AEs) in Safety Population
Assessment method [10] 0 0
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention
Timepoint [10] 0 0
Up to approximately 37.2 months
Secondary outcome [11] 0 0
Number of Participants With Serious Adverse Events (SAEs) in Safety Population
Assessment method [11] 0 0
SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and other situations according to medical or scientific judgement.
Timepoint [11] 0 0
Up to approximately 37.2 months
Secondary outcome [12] 0 0
Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population
Assessment method [12] 0 0
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs).
Timepoint [12] 0 0
Up to approximately 37.2 months
Secondary outcome [13] 0 0
Number of Participants With AEs in Programmed Death Ligand-1 (PD-L1) Combined Positive Score (CPS =1) Population
Assessment method [13] 0 0
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. 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.
Timepoint [13] 0 0
Up to approximately 37.2 months
Secondary outcome [14] 0 0
Number of Participants With SAEs in PD-L1 CPS =1 Population
Assessment method [14] 0 0
SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and other situations according to medical or scientific judgement. 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.
Timepoint [14] 0 0
Up to approximately 37.2 months
Secondary outcome [15] 0 0
Number of Participants With AESIs in PD-L1 CPS =1 Population
Assessment method [15] 0 0
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). 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.
Timepoint [15] 0 0
Up to approximately 37.2 months
Secondary outcome [16] 0 0
Severity of AEs in Safety Population
Assessment method [16] 0 0
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity for each AE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity.
Timepoint [16] 0 0
Up to approximately 37.2 months
Secondary outcome [17] 0 0
Severity of SAEs in Safety Population
Assessment method [17] 0 0
A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. Severity for each SAE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants experiencing SAEs of Grade \>= 3 has been presented.
Timepoint [17] 0 0
Up to approximately 37.2 months
Secondary outcome [18] 0 0
Severity of AESIs in Safety Population
Assessment method [18] 0 0
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Severity of each AESI was reported during the study and was assigned a grade according to the NCI-CTCAE. AESIs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants experiencing AESIs of Grade \>= 3 have been presented.
Timepoint [18] 0 0
Up to approximately 37.2 months
Secondary outcome [19] 0 0
Severity of AEs in PD-L1 CPS =1 Population
Assessment method [19] 0 0
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity for each AE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants experiencing AEs of Grade \>= 3 have been presented. 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.
Timepoint [19] 0 0
Up to approximately 37.2 months
Secondary outcome [20] 0 0
Severity of SAEs in PD-L1 CPS =1 Population
Assessment method [20] 0 0
A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. Severity for each SAE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants that experienced SAEs of Grade \>= 3 have been presented. 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.
Timepoint [20] 0 0
Up to approximately 37.2 months
Secondary outcome [21] 0 0
Severity of AESI in PD-L1 CPS =1 Population
Assessment method [21] 0 0
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Severity of each AESI was reported during the study and was assigned a grade according to the NCI-CTCAE. AESIs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants that experienced AESIs of Grade \>= 3 have been presented.
Timepoint [21] 0 0
Up to approximately 37.2 months
Secondary outcome [22] 0 0
Number of Participants With Dose Modifications in Safety Population
Assessment method [22] 0 0
Number of participants with dose modifications (including dose interruptions, dose delays, dose reductions and treatment discontinuations) were reported by each interventional component.
Timepoint [22] 0 0
Up to approximately 7 months
Secondary outcome [23] 0 0
Number of Participants With Dose Modifications in PD-L1 CPS =1 Population
Assessment method [23] 0 0
Number of participants with dose modifications (including dose interruptions, dose delays, dose reductions and treatment discontinuations) were reported by each interventional component. 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.
Timepoint [23] 0 0
Up to approximately 7 months
Secondary outcome [24] 0 0
Time to Deterioration (TTD) in Pain in mITT Population
Assessment method [24] 0 0
TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the European Organization for Research and Treatment of Cancer Item Library(EORTC IL51) Questionnaire pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC Quality of Life Questionnaire 35-Item Head and Neck Module (QLQ-H\&N35) is a head and neck specific module with multi-item scales. The mouth pain, swallowing, speech problems, opening mouth, coughing, feeding tube, and trouble with social eating domains were administered and referred to as the EORTC IL51. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0-100. A high score represents a high/healthy level of functioning. Kaplan-Meier estimate for the median TTD is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Timepoint [24] 0 0
Up to approximately 7 months
Secondary outcome [25] 0 0
TTD in Pain in PD-L1 CPS =1 Population
Assessment method [25] 0 0
TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the EORTC IL51 pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC QLQ-H\&N35 is a head and neck specific module with multi-item scales. The mouth pain, swallowing, speech problems, opening mouth, coughing, feeding tube, and trouble with social eating domains were administered and referred to as the EORTC IL51. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0-100. A high score represents a high/healthy level of functioning. Kaplan-Meier estimate for the median TTD is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells to the total number of viable tumor cells.
Timepoint [25] 0 0
Up to approximately 7 months
Secondary outcome [26] 0 0
TTD in Physical Function in mITT Population
Assessment method [26] 0 0
TTD in physical function (PF) is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the Patient-Reported Outcomes Measurement Information System - Physical Function (PROMIS PF 8c).The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning.
Timepoint [26] 0 0
Up to approximately 7 months
Secondary outcome [27] 0 0
TTD in Physical Function in PD-L1 CPS =1 Population
Assessment method [27] 0 0
TTD in PF is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the PROMIS PF 8c.The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning. 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
Timepoint [27] 0 0
Up to approximately 7 months

Eligibility
Key inclusion criteria
* 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 1.
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
GSK Investigational Site - Blacktown
Recruitment hospital [2] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [3] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [4] 0 0
GSK Investigational Site - Woolangabba
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
4102 - Woolangabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Argentina
State/province [3] 0 0
Ciudad AutOnoma de Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Oro Verde Entre RIos
Country [5] 0 0
Argentina
State/province [5] 0 0
Rosario
Country [6] 0 0
Argentina
State/province [6] 0 0
San Miguel de TucumAn
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Edegem
Country [9] 0 0
Brazil
State/province [9] 0 0
Curitiba
Country [10] 0 0
Brazil
State/province [10] 0 0
SAo Paulo
Country [11] 0 0
Brazil
State/province [11] 0 0
VitOria
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Denmark
State/province [15] 0 0
Koebenhavn
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux
Country [17] 0 0
France
State/province [17] 0 0
Lyon cedex 08
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
France
State/province [19] 0 0
Poitiers
Country [20] 0 0
France
State/province [20] 0 0
Strasbourg
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Hannover
Country [23] 0 0
Germany
State/province [23] 0 0
Leipzig
Country [24] 0 0
Germany
State/province [24] 0 0
Ulm
Country [25] 0 0
Ireland
State/province [25] 0 0
Dublin
Country [26] 0 0
Italy
State/province [26] 0 0
Brescia
Country [27] 0 0
Italy
State/province [27] 0 0
Firenze
Country [28] 0 0
Italy
State/province [28] 0 0
Milano
Country [29] 0 0
Italy
State/province [29] 0 0
Napoli
Country [30] 0 0
Italy
State/province [30] 0 0
Roma
Country [31] 0 0
Italy
State/province [31] 0 0
Savona
Country [32] 0 0
Japan
State/province [32] 0 0
Osaka
Country [33] 0 0
Japan
State/province [33] 0 0
Tokyo
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Daegu
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Gyeonggi-do
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Hwasun
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Incheon
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul
Country [39] 0 0
Poland
State/province [39] 0 0
Bydgoszcz
Country [40] 0 0
Poland
State/province [40] 0 0
Gdynia
Country [41] 0 0
Poland
State/province [41] 0 0
Gliwice
Country [42] 0 0
Poland
State/province [42] 0 0
Lublin
Country [43] 0 0
Poland
State/province [43] 0 0
Tomaszow Mazowiecki
Country [44] 0 0
Poland
State/province [44] 0 0
Warszawa
Country [45] 0 0
Romania
State/province [45] 0 0
Bucuresti
Country [46] 0 0
Romania
State/province [46] 0 0
Cluj Napoca
Country [47] 0 0
Romania
State/province [47] 0 0
Craiova
Country [48] 0 0
Romania
State/province [48] 0 0
Floresti
Country [49] 0 0
Romania
State/province [49] 0 0
Otopeni
Country [50] 0 0
Romania
State/province [50] 0 0
Suceava
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Pushkin
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Spain
State/province [54] 0 0
Valencia
Country [55] 0 0
Sweden
State/province [55] 0 0
Stockholm
Country [56] 0 0
United Kingdom
State/province [56] 0 0
London
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Nottingham
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.