Neoplasms, Head and Neck
Conditions
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
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.
Interventions
DRUGfeladilimab
feladilimab is available as an intravenous infusion.
DRUGPembrolizumab
Pembrolizumab is available as an intravenous infusion.
DRUGPlacebo
Placebo is available as an intravenous infusion.
Sponsors
Merck Sharp & Dohme LLC
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a double blind study.
Intervention model description
This will be a randomized, parallel group treatment study with eligible participants receiving GSK3359609 plus pembrolizumab or placebo plus pembrolizumab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population | Up to approximately 16 months | 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. |
| OS in the PD-L1 Expression High (CPS ≥20) Population | Up to approximately 16 months | 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. |
| Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population | Up to approximately 16 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population | 12 months | 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. |
| Milestone OS Rate at 24 Months in the PD-L1 CPS ≥1 Population | 24 months | 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. |
| Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population | 12 months | 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. |
| Milestone OS Rate at 24 Months in the PD-L1 CPS ≥20 Population | 24 months | 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. |
| Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | Up to approximately 16 months | 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. |
| ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | Up to approximately 16 months | 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. |
| Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | Up to approximately 16 months | 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. |
| Number of Participants With Adverse Events of Special Interest (AESI) | Up to approximately 43 months | 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. |
| DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | Up to approximately 16 months | 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. |
| Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | Up to approximately 16 months | 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. |
| PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population | Up to approximately 16 months | 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. |
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 43 months | 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. |
| Number of Participants With AEs by Severity | Up to approximately 43 months | 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. |
| Number of Participants With SAEs by Severity | Up to approximately 43 months | 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. |
| Number of Participants With AESI by Severity | Up to approximately 43 months | 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. |
| Number of Participants With Dose Modifications | Up to approximately 16 months | Number of participants with dose modifications (including dose interruptions, dose delays and treatment discontinuations) were reported by each interventional component. |
| Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population | Up to approximately 16 months | 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. |
| TTD in Pain in the PD-L1 CPS ≥20 Population | Up to approximately 16 months | 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. |
| TTD in Physical Function in the PD-L1 CPS ≥1 Population | Up to approximately 16 months | 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. |
| TTD in Physical Function in the PD-L1 CPS ≥20 Population | Up to approximately 16 months | 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. |
| DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | Up to approximately 16 months | 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. |
| PFS Per RECIST in the PD-L1 CPS ≥20 Population | Up to approximately 16 months | 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. |
| PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population | Up to approximately 16 months | 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. |
Countries
Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russia, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
A total of 315 participants with recurrent or metastatic head and neck squamous cell carcinoma/cancer (HNSCC) were enrolled in this study.
Pre-assignment details
Recruitment in the study was stopped following review of interim safety and efficacy data by the Independent Data Monitoring Committee, after a pre-specified futility analysis. A Dear Investigator Letter (DIL) was issued to stop screening/randomization of further subjects to the study.
Participants by arm
| Arm | Count |
|---|---|
| Participants Receiving Feladilimab and Pembrolizumab Participants were administered feladilimab (GSK3359609-humanized anti-ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion Q3W. | 158 |
| Participants Receiving Placebo and Pembrolizumab Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion Q3W. | 157 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 7 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Study Closed/Terminated | 26 | 38 |
| Overall Study | Withdrawal by Subject | 12 | 11 |
Baseline characteristics
| Characteristic | Participants Receiving Feladilimab and Pembrolizumab | Participants Receiving Placebo and Pembrolizumab | Total |
|---|---|---|---|
| Age, Customized 18-64 years | 95 Participants | 79 Participants | 174 Participants |
| Age, Customized ≥65-84 years | 62 Participants | 76 Participants | 138 Participants |
| Age, Customized ≥85 years | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 19 Participants | 22 Participants | 41 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 12 Participants | 7 Participants | 19 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Missing | 3 Participants | 6 Participants | 9 Participants |
| Race/Ethnicity, Customized Mixed White Race | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 111 Participants | 118 Participants | 229 Participants |
| Sex: Female, Male Female | 29 Participants | 31 Participants | 60 Participants |
| Sex: Female, Male Male | 129 Participants | 126 Participants | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 116 / 159 | 97 / 156 |
| other Total, other adverse events | 125 / 159 | 128 / 156 |
| serious Total, serious adverse events | 52 / 159 | 53 / 156 |
Outcome results
Primary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | OS in the PD-L1 Expression High (CPS ≥20) Population | 42.1 Week |
| Participants Receiving Placebo and Pembrolizumab | OS in the PD-L1 Expression High (CPS ≥20) Population | NA Week |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).p-value: >0.99995% CI: [2.01, 9.82]Stratified Cox proportional hazard model
Primary
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
Population: mITT: All randomized participants, whether or not randomized intervention was administered, excluding those who were first dosed or randomized after the date of DIL requesting immediate discontinuation of feladilimab /placebo. This analysis was based on the study intervention to which the participant was randomized. All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population | 44.1 Week |
| Participants Receiving Placebo and Pembrolizumab | Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population | NA Week |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS \<20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).p-value: 0.97395% CI: [0.99, 2.29]Stratified Cox proportional hazard model
Primary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population | 10.1 Week |
| Participants Receiving Placebo and Pembrolizumab | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population | 16.0 Week |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS \<20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).p-value: 0.98995% CI: [1.05, 1.86]Stratified Cox proportional hazard model
Secondary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | 37.1 Percentage of Participants |
| Participants Receiving Placebo and Pembrolizumab | DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | 55.1 Percentage of Participants |
Comparison: The comparison between treatment groups was based on the stratified Miettinen \& Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.95% CI: [-33.7, -1.4]
Secondary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | 33.1 Percentage of Participants |
| Participants Receiving Placebo and Pembrolizumab | Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | 44.9 Percentage of Participants |
Comparison: The comparison between treatment groups was based on the stratified Miettinen \& Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included PD-L1 expression (CPS ≥20 vs. 1≤ CPS \<20) and HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.95% CI: [-22.4, -1.1]
Secondary
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
Population: Data for participants with a best overall response of CR or PR in the mITT population with PD-L1 CPS ≥20 are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | NA Weeks |
| Participants Receiving Placebo and Pembrolizumab | DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | NA Weeks |
Secondary
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
Population: Data for participants with a best overall response of CR or PR in the mITT population with PD-L1 CPS ≥1 are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | NA Weeks |
| Participants Receiving Placebo and Pembrolizumab | Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | NA Weeks |
Secondary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population | 44.0 Percentage of participants |
| Participants Receiving Placebo and Pembrolizumab | Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population | 68.0 Percentage of participants |
Secondary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population | 46.0 Percentage of participants |
| Participants Receiving Placebo and Pembrolizumab | Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population | 88.0 Percentage of participants |
Secondary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were to be analyzed. Data for this endpoint were not collected as all participants were on the study for \< 24 months, the maximum duration of follow-up was approximately 16 months.
Secondary
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
Population: Participants with PD-L1 CPS ≥20 in the mITT population were to be analyzed. Data for this endpoint were not collected as all participants were on the study for \<24 months, the maximum duration of follow-up was approximately 16 months.
Secondary
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
Population: All participants in the safety population were analyzed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Adverse Events of Special Interest (AESI) | 49 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Adverse Events of Special Interest (AESI) | 67 Participants |
Secondary
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
Population: Safety Population: All randomized participants who take at least 1 dose of study intervention
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With AEs by Severity | Grade 1 | 34 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With AEs by Severity | Grade 3 | 46 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With AEs by Severity | Grade 2 | 48 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With AEs by Severity | Grade 4 | 7 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With AEs by Severity | Grade 5 | 15 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With AEs by Severity | Grade 2 | 54 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With AEs by Severity | Grade 3 | 46 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With AEs by Severity | Grade 5 | 18 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With AEs by Severity | Grade 1 | 21 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With AEs by Severity | Grade 4 | 6 Participants |
Secondary
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
Population: All participants in the safety population were analyzed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With AESI by Severity | 2 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With AESI by Severity | 6 Participants |
Secondary
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
Population: Safety Population: All randomized participants who take at least 1 dose of study intervention. Participants were assigned to the actual study intervention group of feladilimab + pembrolizumab if the participant received any dose of feladilimab. Participants were analyzed according to the actual study intervention received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 150 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 52 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 145 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 53 Participants |
Secondary
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
Population: All participants in the safety population were analyzed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Dose interruption by component - placebo | NA Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Dose interruption by component - pembrolizumab | 0 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Treatment discontinuation by component - feladilimab/placebo | 159 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Treatment discontinuation by component - pembrolizumab | 108 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Dose interruption by component - feladilimab | 4 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Dose delays by component - feladilimab | 9 Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Dose delays by component - placebo | NA Participants |
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With Dose Modifications | Dose delays by component - pembrolizumab | 11 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Dose delays by component - feladilimab | NA Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Dose interruption by component - placebo | 1 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Dose interruption by component - feladilimab | NA Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Dose delays by component - placebo | 5 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Dose interruption by component - pembrolizumab | 1 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Treatment discontinuation by component - feladilimab/placebo | 154 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Dose delays by component - pembrolizumab | 6 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With Dose Modifications | Treatment discontinuation by component - pembrolizumab | 93 Participants |
Secondary
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
Population: Safety Population: All randomized participants who take at least 1 dose of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Number of Participants With SAEs by Severity | 43 Participants |
| Participants Receiving Placebo and Pembrolizumab | Number of Participants With SAEs by Severity | 46 Participants |
Secondary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | 20.0 Percentage of Participants |
| Participants Receiving Placebo and Pembrolizumab | ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population | 33.3 Percentage of Participants |
Comparison: The comparison between the treatment groups was based on the stratified Miettinen \& Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.95% CI: [-27.8, 1.5]
Secondary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | 19.7 Percentage of Participants |
| Participants Receiving Placebo and Pembrolizumab | Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population | 25.0 Percentage of Participants |
Comparison: The comparison between the treatment groups was based on the stratified Miettinen \& Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included PD-L1 expression (CPS ≥20 vs. 1≤ CPS \<20) and HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.95% CI: [-14.6, 4]
Secondary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population | 13.0 Week |
| Participants Receiving Placebo and Pembrolizumab | PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population | 21.4 Week |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS \<20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)p-value: 0.99695% CI: [1.1, 1.99]Stratified Cox proportional hazard model
Secondary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population | 13.1 Week |
| Participants Receiving Placebo and Pembrolizumab | PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population | 26.7 Week |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).95% CI: [1, 2.53]Stratified Cox proportional hazard model
Secondary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | PFS Per RECIST in the PD-L1 CPS ≥20 Population | 13.0 Week |
| Participants Receiving Placebo and Pembrolizumab | PFS Per RECIST in the PD-L1 CPS ≥20 Population | 21.1 Week |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)95% CI: [0.98, 2.43]Stratified Cox proportional hazard model
Secondary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population | 6.3 Months |
| Participants Receiving Placebo and Pembrolizumab | Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population | 10.4 Months |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS \<20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).p-value: 0.78395% CI: [0.78, 1.77]Stratified Cox proportional hazard model
Secondary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | TTD in Pain in the PD-L1 CPS ≥20 Population | NA Months |
| Participants Receiving Placebo and Pembrolizumab | TTD in Pain in the PD-L1 CPS ≥20 Population | 12 Months |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).p-value: 0.595% CI: [0.5, 2]Stratified Cox proportional hazard model
Secondary
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
Population: All participants with PD-L1 CPS ≥1 in the mITT population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | TTD in Physical Function in the PD-L1 CPS ≥1 Population | 4.9 Months |
| Participants Receiving Placebo and Pembrolizumab | TTD in Physical Function in the PD-L1 CPS ≥1 Population | 4.9 Months |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS \<20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).p-value: 0.32995% CI: [0.62, 1.34]Stratified Cox proportional hazard model
Secondary
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
Population: Data for participants with PD-L1 CPS ≥20 in mITT population are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Feladilimab and Pembrolizumab | TTD in Physical Function in the PD-L1 CPS ≥20 Population | 4.9 Months |
| Participants Receiving Placebo and Pembrolizumab | TTD in Physical Function in the PD-L1 CPS ≥20 Population | 4.9 Months |
Comparison: The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).p-value: 0.60895% CI: [0.6, 2]Stratified Cox proportional hazard model