Clinical Trials List
Protocol Number209229
NCT Number(ClinicalTrials.gov Identfier)NCT04128696
2020-01-31 - 2023-10-03
Phase II/III
Recruiting7
ICD-10C44.529
Squamous cell carcinoma of skin of other part of trunk
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
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
GlaxoSmithKline
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 劉奕廷 Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- 顏志傑 Division of General Internal Medicine
- Kwang-Yu Chang 國衛院
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 張平穎 Division of Hematology & Oncology
- 吳宜穎 Division of Hematology & Oncology
- 戴明燊 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
- 黃子權 Division of Hematology & Oncology
- 賴學緯 Division of Hematology & Oncology
- 陳宇欽 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ling-Wei Wang Division of Hematology & Oncology
- Mu-Hsin Chang Division of Hematology & Oncology
- 陳盛裕 未分科
- Sheng-Yu Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Hsiang-Fong Kao Division of Hematology & Oncology
- YA-FANG CHEN Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- HUAI-CHENG HUANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
PD-L1 Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Objectives
Primary Objectives
Compare the efficacy of GSK3359609 in
combination with pembrolizumab to
pembrolizumab plus placebo in the
Programmed Death Ligand 1 (PD L1)
expression positive (CPS 1) population and
in the PD-L1 expression high (CPS 20)
population
Secondary Objectives
Further compare the efficacy of
GSK3359609 in combination with
pembrolizumab compared with
pembrolizumab plus placebo
Evaluate the safety and tolerability of
GSK3359609 in combination with
pembrolizumab compared with
pembrolizumab plus placebo
Evaluate and compare disease related
symptoms and impact on function and
health-related quality of life (HRQoL) of
GSK3359609/pembrolizumab versus
pembrolizumab plus placebo
Test Drug
GSK3359609
Active Ingredient
GSK3359609
Dosage Form
8ml/vial
Dosage
10 mg/mL
Endpoints
Primary Outcome Measures :
Overall survival (OS) in the PD-L1 expression positive (CPS >=1) population [ Time Frame: Up to 4 years ]
OS is defined as the time from the date of randomization to the date of death due to any cause.
OS in the PD-L1 expression high (CPS >=20) population [ Time Frame: Up to 4 years ]
OS is defined as the time from the date of randomization to the date of death due to any cause.
Progression-free survival (PFS) in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
PFS is 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.
Secondary Outcome Measures :
PFS per immune-based RECIST (iRECIST) in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
PFS per iRECIST is defined as the time from the date of randomization to the date of first documented disease progression confirmed consecutively per iRECIST.
PFS per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
PFS per RECIST v1.1 is defined as the time from the date of randomization to the date of first documented disease progression per RECIST v1.1.
PFS per iRECIST (iPFS) in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
PFS per iRECIST is defined as the time from the date of randomization to the date of first documented disease progression confirmed consecutively per iRECIST.
Milestone OS rate at 12 months in the PD-L1 CPS >=1 population [ Time Frame: Up to 12 months ]
Milestone OS rate at 12 months will be evaluated from the survival curves.
Milestone OS rate at 24 months in the PD-L1 CPS >=1 population [ Time Frame: Up to 24 months ]
Milestone OS rate at 24 months will be evaluated from the survival curves.
Milestone OS rate at 12 months in the PD-L1 CPS >=20 population [ Time Frame: Up to 12 months ]
Milestone OS rate at 12 months will be evaluated from the survival curves.
Milestone OS rate at 24 months in the PD-L1 CPS >=20 population [ Time Frame: Up to 24 months ]
Milestone OS rate at 24 months will be evaluated from the survival curves.
Overall response rate (ORR) per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
ORR is 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.
ORR per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
ORR is defined as the proportion of the participants who have a CR or PR as the best overall response per RECIST v1.1.
Disease control rate (DCR) per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
DCR is 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 per RECIST v1.1.
DCR per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
DCR is defined as the percentage of participants with a best overall response of CR or PR at any time plus SD meeting the minimum time of 15 weeks per RECIST v1.1.
Duration of response (DoR) per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.
DoR per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.
Number of participants with any adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 4 years ]
Number of participants with any adverse events (AEs) and serious adverse events (SAEs) per ICH definitions.
Number of participants with adverse events of special interest (AESI) [ Time Frame: Up to 4 years ]
AESI are defined as events of potential immunologic etiology, including immune-related AEs (irAEs).
Number of participants with dose modifications [ Time Frame: Up to 4 years ]
Number of participants with dose modifications (i.e. interruptions, discontinuations) will be reported.
Time to deterioration in pain in the PD-L1 CPS >=1 population [ Time Frame: Up to 4 years ]
The time to deterioration in pain will be measured by structured patients questionnaire.
Time to deterioration in pain in the PD-L1 CPS >=20 population [ Time Frame: Up to 4 years ]
Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured patients questionnaire.
Time to deterioration in physical function in the PD-L1 CPS >=1 population [ Time Frame: Up to 4 years ]
The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.
Time to deterioration in physical function in the PD-L1 CPS >=20 population [ Time Frame: Up to 4 years ]
Time to deterioration in physical function is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured patients questionnaire.
Overall survival (OS) in the PD-L1 expression positive (CPS >=1) population [ Time Frame: Up to 4 years ]
OS is defined as the time from the date of randomization to the date of death due to any cause.
OS in the PD-L1 expression high (CPS >=20) population [ Time Frame: Up to 4 years ]
OS is defined as the time from the date of randomization to the date of death due to any cause.
Progression-free survival (PFS) in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
PFS is 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.
Secondary Outcome Measures :
PFS per immune-based RECIST (iRECIST) in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
PFS per iRECIST is defined as the time from the date of randomization to the date of first documented disease progression confirmed consecutively per iRECIST.
PFS per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
PFS per RECIST v1.1 is defined as the time from the date of randomization to the date of first documented disease progression per RECIST v1.1.
PFS per iRECIST (iPFS) in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
PFS per iRECIST is defined as the time from the date of randomization to the date of first documented disease progression confirmed consecutively per iRECIST.
Milestone OS rate at 12 months in the PD-L1 CPS >=1 population [ Time Frame: Up to 12 months ]
Milestone OS rate at 12 months will be evaluated from the survival curves.
Milestone OS rate at 24 months in the PD-L1 CPS >=1 population [ Time Frame: Up to 24 months ]
Milestone OS rate at 24 months will be evaluated from the survival curves.
Milestone OS rate at 12 months in the PD-L1 CPS >=20 population [ Time Frame: Up to 12 months ]
Milestone OS rate at 12 months will be evaluated from the survival curves.
Milestone OS rate at 24 months in the PD-L1 CPS >=20 population [ Time Frame: Up to 24 months ]
Milestone OS rate at 24 months will be evaluated from the survival curves.
Overall response rate (ORR) per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
ORR is 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.
ORR per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
ORR is defined as the proportion of the participants who have a CR or PR as the best overall response per RECIST v1.1.
Disease control rate (DCR) per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
DCR is 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 per RECIST v1.1.
DCR per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
DCR is defined as the percentage of participants with a best overall response of CR or PR at any time plus SD meeting the minimum time of 15 weeks per RECIST v1.1.
Duration of response (DoR) per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 3 years ]
DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.
DoR per RECIST v1.1 in the PD-L1 CPS >=20 population [ Time Frame: Up to 3 years ]
DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.
Number of participants with any adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 4 years ]
Number of participants with any adverse events (AEs) and serious adverse events (SAEs) per ICH definitions.
Number of participants with adverse events of special interest (AESI) [ Time Frame: Up to 4 years ]
AESI are defined as events of potential immunologic etiology, including immune-related AEs (irAEs).
Number of participants with dose modifications [ Time Frame: Up to 4 years ]
Number of participants with dose modifications (i.e. interruptions, discontinuations) will be reported.
Time to deterioration in pain in the PD-L1 CPS >=1 population [ Time Frame: Up to 4 years ]
The time to deterioration in pain will be measured by structured patients questionnaire.
Time to deterioration in pain in the PD-L1 CPS >=20 population [ Time Frame: Up to 4 years ]
Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured patients questionnaire.
Time to deterioration in physical function in the PD-L1 CPS >=1 population [ Time Frame: Up to 4 years ]
The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.
Time to deterioration in physical function in the PD-L1 CPS >=20 population [ Time Frame: Up to 4 years ]
Time to deterioration in physical function is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured patients questionnaire.
Inclution Criteria
Inclusion Criteria:
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 IHC CPS 1 status by central laboratory testing
Have results from testing of Human Papilloma Virus (HPV) status for oropharyngeal cancer
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 IHC CPS 1 status by central laboratory testing
Have results from testing of Human Papilloma Virus (HPV) status for oropharyngeal cancer
Exclusion Criteria
Exclusion Criteria:
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.
Toxicity from previous anticancer treatment that includes 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
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.
Toxicity from previous anticancer treatment that includes 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
The Estimated Number of Participants
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Taiwan
20 participants
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Global
600 participants
