A Phase 3 interventional study of feladilimab and Pembrolizumab in Neoplasms, Head and Neck, sponsored by GlaxoSmithKline. Terminated at 164 sites in 26 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-10.
Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment
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.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 315 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
Counted across the registry records on this site, refreshed daily.
Female participants: must not be pregnant, not breastfeeding, and at least one of the following conditions apply:
Exclusion Criteria:
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
Participants were administered feladilimab (humanized anti-ICOS immunoglobulin G4 \[IgG4\] monoclonal antibody \[mAb\]) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an intravenous (IV) infusion once every three weeks.
Drug: feladilimab · Drug: Pembrolizumab
Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion once every three weeks.
Drug: Pembrolizumab · Drug: Placebo
feladilimab is available as an intravenous infusion.
Pembrolizumab is available as an intravenous infusion.
Placebo is available as an intravenous infusion.
Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
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.
Time frame: Up to approximately 16 months
OS in the PD-L1 Expression High (CPS ≥20) Population
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.
Time frame: Up to approximately 16 months
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population
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.
Time frame: Up to approximately 16 months
PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population
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.
Time frame: Up to approximately 16 months
PFS Per RECIST in the PD-L1 CPS ≥20 Population
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.
Time frame: Up to approximately 16 months
PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population
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.
Time frame: Up to approximately 16 months
Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population
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.
Time frame: 12 months
Milestone OS Rate at 24 Months in the PD-L1 CPS ≥1 Population
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.
Time frame: 24 months
Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population
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.
Time frame: 12 months
Milestone OS Rate at 24 Months in the PD-L1 CPS ≥20 Population
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.
Time frame: 24 months
Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
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.
Time frame: Up to approximately 16 months
ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
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.
Time frame: Up to approximately 16 months
Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
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.
Time frame: Up to approximately 16 months
DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
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.
Time frame: Up to approximately 16 months
Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
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.
Time frame: Up to approximately 16 months
DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
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.
Time frame: Up to approximately 16 months
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Up to approximately 43 months
Number of Participants With AEs by Severity
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.
Time frame: Up to approximately 43 months
Number of Participants With SAEs by Severity
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.
Time frame: Up to approximately 43 months
Number of Participants With Adverse Events of Special Interest (AESI)
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.
Time frame: Up to approximately 43 months
Number of Participants With AESI by Severity
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.
Time frame: Up to approximately 43 months
Number of Participants With Dose Modifications
Number of participants with dose modifications (including dose interruptions, dose delays and treatment discontinuations) were reported by each interventional component.
Time frame: Up to approximately 16 months
Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population
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.
Time frame: Up to approximately 16 months
TTD in Pain in the PD-L1 CPS ≥20 Population
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.
Time frame: Up to approximately 16 months
TTD in Physical Function in the PD-L1 CPS ≥1 Population
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.
Time frame: Up to approximately 16 months
TTD in Physical Function in the PD-L1 CPS ≥20 Population
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.
Time frame: Up to approximately 16 months
A total of 315 participants with recurrent or metastatic head and neck squamous cell carcinoma/cancer (HNSCC) were enrolled in this study.
| Milestone | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Started | 158 | 157 |
| Modified intent to treat (mitt) population | 157 | 156 |
| Safety population | 159 | 156 |
| Completed | 115 | 98 |
| Not completed | 43 | 59 |
| Withdrew: Lost to follow-up | 3 | 7 |
| Withdrew: Withdrawal by subject | 12 | 11 |
| Withdrew: Study closed/terminated | 26 | 38 |
| Withdrew: Physician decision | 2 | 3 |
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.
| Week | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population | 44.1 (35.9 to NA) | NA (52.4 to NA) |
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.
| Week | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| OS in the PD-L1 Expression High (CPS ≥20) Population | 42.1 (25.4 to NA) | NA (52.4 to NA) |
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.
| Week | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population | 10.1 (9.1 to 15.0) | 16.0 (14.3 to 26.1) |
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.
| Week | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population | 13.0 (9.1 to 15.1) | 21.4 (15.6 to 27.0) |
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.
| Week | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| PFS Per RECIST in the PD-L1 CPS ≥20 Population | 13.0 (8.6 to 26.1) | 21.1 (15.6 to 32.9) |
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.
| Week | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population | 13.1 (8.6 to 26.7) | 26.7 (20.1 to 32.9) |
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.
| Percentage of participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population | 44.0 (30.0 to 58.0) | 68.0 (57.0 to 77.0) |
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.
No measurements were reported for this outcome.
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.
| Percentage of participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population | 46.0 (28.0 to 63.0) | 88.0 (76.0 to 94.0) |
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.
No measurements were reported for this outcome.
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.
| Percentage of Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | 19.7 (13.8 to 26.8) | 25.0 (18.4 to 32.6) |
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.
| Percentage of Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | 20.0 (11.4 to 31.3) | 33.3 (22.4 to 45.7) |
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.
| Percentage of Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | 33.1 (25.8 to 41.1) | 44.9 (36.9 to 53.0) |
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.
| Percentage of Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | 37.1 (25.9 to 49.5) | 55.1 (42.6 to 67.1) |
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.
| Weeks | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | NA (NA to NA) | NA (20.6 to NA) |
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.
| Weeks | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | NA (18.1 to NA) | NA (12.1 to NA) |
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.
| Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Any AE | 150 | 145 |
| Any SAE | 52 | 53 |
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.
| Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Grade 1 | 34 | 21 |
| Grade 2 | 48 | 54 |
| Grade 3 | 46 | 46 |
| Grade 4 | 7 | 6 |
| Grade 5 | 15 | 18 |
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.
| Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Number of Participants With SAEs by Severity | 43 | 46 |
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.
| Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Number of Participants With Adverse Events of Special Interest (AESI) | 49 | 67 |
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.
| Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Number of Participants With AESI by Severity | 2 | 6 |
Number of participants with dose modifications (including dose interruptions, dose delays and treatment discontinuations) were reported by each interventional component.
| Participants | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Dose interruption by component - feladilimab | 4 | NA |
| Dose interruption by component - placebo | NA | 1 |
| Dose interruption by component - pembrolizumab | 0 | 1 |
| Dose delays by component - feladilimab | 9 | NA |
| Dose delays by component - placebo | NA | 5 |
| Dose delays by component - pembrolizumab | 11 | 6 |
| Treatment discontinuation by component - feladilimab/placebo | 159 | 154 |
| Treatment discontinuation by component - pembrolizumab | 108 | 93 |
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.
| Months | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population | 6.3 (5.1 to NA) | 10.4 (6.3 to NA) |
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.
| Months | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| TTD in Pain in the PD-L1 CPS ≥20 Population | NA (5.1 to NA) | 12 (6.3 to NA) |
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.
| Months | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| TTD in Physical Function in the PD-L1 CPS ≥1 Population | 4.9 (3.5 to 7.7) | 4.9 (3.0 to 6.3) |
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.
| Months | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| TTD in Physical Function in the PD-L1 CPS ≥20 Population | 4.9 (2.1 to NA) | 4.9 (3.1 to NA) |
Collected over All cause mortality, non-SAEs and SAEs were collected from Day 1 to up to approximately 43 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | 116/159 (73%) | 52/159 (32.7%) | 125/159 (78.6%) |
| Participants Receiving Placebo and Pembrolizumab | 97/156 (62.2%) | 53/156 (34%) | 128/156 (82.1%) |
| Event | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| Tumour haemorrhageNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 4/159 | 6/156 |
| DysphagiaGastrointestinal disorders | 2/159 | 4/156 |
| COVID-19Infections and infestations | 2/159 | 4/156 |
| PneumoniaInfections and infestations | 4/159 | 4/156 |
| Pneumonia aspirationInfections and infestations | 4/159 | 4/156 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 4/159 | 3/156 |
| HypercalcaemiaMetabolism and nutrition disorders | 2/159 | 3/156 |
| MalnutritionMetabolism and nutrition disorders | 0/159 | 3/156 |
| General physical health deteriorationGeneral disorders | 3/159 | 1/156 |
| SyncopeNervous system disorders | 3/159 | 1/156 |
| Event | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab |
|---|---|---|
| FatigueGeneral disorders | 29/159 | 29/156 |
| Decreased appetiteMetabolism and nutrition disorders | 15/159 | 28/156 |
| Weight decreasedInvestigations | 20/159 | 27/156 |
| AnaemiaBlood and lymphatic system disorders | 26/159 | 21/156 |
| ConstipationGastrointestinal disorders | 22/159 | 24/156 |
| RashSkin and subcutaneous tissue disorders | 9/159 | 21/156 |
| DiarrhoeaGastrointestinal disorders | 21/159 | 13/156 |
| HypothyroidismEndocrine disorders | 20/159 | 16/156 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 17/159 | 19/156 |
| NauseaGastrointestinal disorders | 17/159 | 17/156 |
| Age, Customized(Participants) | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab | Total |
|---|---|---|---|
| 18-64 years | 95 | 79 | 174 |
| ≥65-84 years | 62 | 76 | 138 |
| ≥85 years | 1 | 2 | 3 |
| Sex: Female, Male(Participants) | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab | Total |
|---|---|---|---|
| Female | 29 | 31 | 60 |
| Male | 129 | 126 | 255 |
| Race/Ethnicity, Customized(Participants) | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab | Total |
|---|---|---|---|
| Asian - Central/South Asian Heritage | 2 | 0 | 2 |
| Asian - East Asian Heritage | 19 | 22 | 41 |
| Asian - Japanese Heritage | 12 | 7 | 19 |
| Black or African American | 4 | 2 | 6 |
| Missing | 3 | 6 | 9 |
| Mixed White Race | 1 | 1 | 2 |
| Multiple | 1 | 0 | 1 |
| White - Arabic/North African Heritage | 4 | 1 | 5 |
| White - White/Caucasian/European Heritage | 111 | 118 | 229 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
Showing the first 100 of 164 sites across 26 countries.
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Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.
Supporting information: Study protocol, Sap, Icf, Csr
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