Brief Summary
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.
Brief Title
Study of GSK3359609 and Pembrolizumab in Programmed Death Receptor 1-ligand 1 (PD-L1) Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Categories
Completion Date
Completion Date Type
Actual
Conditions
Neoplasms, Head and Neck
Eligibility 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:
1. Not a woman of childbearing potential (WOCBP)
2. 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
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
* 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
* 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:
1. Not a woman of childbearing potential (WOCBP)
2. 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
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
* 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
Inclusion 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:
1. Not a woman of childbearing potential (WOCBP)
2. 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
* 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:
1. Not a woman of childbearing potential (WOCBP)
2. 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
Gender
All
Gender Based
false
Keywords
GSK3359609
Pembrolizumab
Programmed death receptor 1-ligand 1
Head and neck squamous cell carcinoma/cancer
Inducible T cell co-stimulatory receptor
Keynote-A01
Head & neck
Phase III
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04128696
Org Class
Industry
Org Full Name
GlaxoSmithKline
Org Study Id
209229
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
Outcome Time Frame
Up to approximately 16 months
Outcome Description
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.
Outcome Measure
OS in the PD-L1 Expression High (CPS ≥20) Population
Outcome Time Frame
Up to approximately 16 months
Outcome Description
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.
Outcome Measure
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population
Outcome Time Frame
Up to approximately 16 months
Secondary Ids
Secondary Id
2019-002263-99
Secondary Outcomes
Outcome Description
PFS per iRECIST was defined as the interval of time from the date of randomization to the date of the first documented disease progression confirmed consecutively per iRECIST based on investigator assessment, 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population
Outcome Description
PFS per RECIST v1.1 was defined as the time from the date of randomization to the date of first documented disease progression per RECIST v1.1. 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
PFS Per RECIST in the PD-L1 CPS ≥20 Population
Outcome Description
PFS per iRECIST was defined as the interval of time from the date of randomization to the date of the first documented disease progression confirmed consecutively per iRECIST based on investigator assessment, 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population
Outcome Description
Milestone OS rate at 12 months was estimated using the Kaplan-Meier method. Associated 95% confidence intervals are 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.
Outcome Time Frame
12 months
Outcome Measure
Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population
Outcome Description
Milestone OS rate at 24 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.
Outcome Time Frame
24 months
Outcome Measure
Milestone OS Rate at 24 Months in the PD-L1 CPS ≥1 Population
Outcome Description
Milestone OS rate at 12 months was estimated using the Kaplan-Meier method. Associated 95% confidence intervals are 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.
Outcome Time Frame
12 months
Outcome Measure
Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population
Outcome Description
Milestone OS rate at 24 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.
Outcome Time Frame
24 months
Outcome Measure
Milestone OS Rate at 24 Months in the PD-L1 CPS ≥20 Population
Outcome Description
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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
Outcome Description
ORR per RECIST v1.1 was defined as the proportion of the participants who have a CR or 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
Outcome Description
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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
Outcome Description
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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
Outcome Description
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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
Outcome Description
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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
Outcome Description
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. An SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement.
Outcome Time Frame
Up to approximately 43 months
Outcome Measure
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Outcome Description
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 of each AE was reported during the study and was assigned a grade according to the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE). AEs 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.
Outcome Time Frame
Up to approximately 43 months
Outcome Measure
Number of Participants With AEs by Severity
Outcome Description
An SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results 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 of each SAE was reported during the study and was assigned a grade according to the NCI-CTCAE. SAEs 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 SAEs of Grade ≥3 have been presented.
Outcome Time Frame
Up to approximately 43 months
Outcome Measure
Number of Participants With SAEs by Severity
Outcome Description
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated.
Outcome Time Frame
Up to approximately 43 months
Outcome Measure
Number of Participants With Adverse Events of Special Interest (AESI)
Outcome Description
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated. 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.
Outcome Time Frame
Up to approximately 43 months
Outcome Measure
Number of Participants With AESI by Severity
Outcome Description
Number of participants with dose modifications (including dose interruptions, dose delays and treatment discontinuations) were reported by each interventional component.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
Number of Participants With Dose Modifications
Outcome Description
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) 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 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. 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population
Outcome Description
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. 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
TTD in Pain in the PD-L1 CPS ≥20 Population
Outcome Description
TTD in physical function 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
TTD in Physical Function in the PD-L1 CPS ≥1 Population
Outcome Description
TTD in physical function 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. Data are presented for the PD-L1 CPS \>=1 participants from mITT population. 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.
Outcome Time Frame
Up to approximately 16 months
Outcome Measure
TTD in Physical Function in the PD-L1 CPS ≥20 Population
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Enrico Castellucci
Investigator Email
ecastell@montefiore.org
Investigator Phone