Metastatic Head and Neck Cancer, Recurrent Head and Neck Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1),, Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2), chemotherapy, 5-fluorouracil, cisplatin, carboplatin
Brief summary
Participants with recurrent or metastatic (R/M) squamous cell cancer of the head and neck (HNSCC) will be randomly assigned to receive pembrolizumab monotherapy \[pembro mono\], pembrolizumab plus chemotherapy with a platinum-based drug (cisplatin or carboplatin) and 5-Fluorouracil (5-FU) \[pembro combo\], or cetuximab plus a platinum-based drug (cisplatin or carboplatin) and 5-FU \[control\]. The overall primary study hypotheses are as follows in all participants and in participants with Programmed Cell Death Ligand 1 (PD-L1) positive expression defined by Combined Positive Score (CPS) ≥1 and CPS ≥20: 1) pembrolizumab monotherapy prolongs progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by Blinded Independent Central Review (BICR) and prolongs overall survival (OS) compared to standard treatment, and 2) pembrolizumab combination with chemotherapy prolongs PFS per RECIST 1.1 assessed by BICR and prolongs OS compared to standard treatment.
Detailed description
The 12 primary superiority hypotheses will be evaluated by comparing the pembro mono arm or pembro combo arm separately to the control arm, for PFS and OS in all first line (1L) R/M HNSCC participants and in 1L R/M HNSCC participants with positive PD-L1 expression (PD-L1 CPS ≥1 and CPS ≥20). Per protocol, response/progression or adverse events (AEs) that occur during the second pembrolizumab course will not be counted towards efficacy outcome measures or safety outcome measures, respectively.
Interventions
BIOLOGICALPembrolizumab
Pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 35 cycles (up to \ 2 years).
DRUGCisplatin
Cisplatin 100 mg/m\^2 IV on Day 1 of each 3-week cycle (6 cycle maximum \[up to \ 4 months\]).
DRUGCarboplatin
Carboplatin at a target AUC 5 IV on Day 1 of each 3-week cycle (6 cycle maximum \[up to \ 4 months\]).
DRUG5-FU
5-FU 1000 mg/m\^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum \[up to \ 4 months\]).
BIOLOGICALCetuximab
Cetuximab on Day 1 at a dose of 400 mg/m\^2 IV, and then 250 mg/m\^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically- or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma considered incurable by local therapies * No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed \> 6 months prior if given as part of multimodal treatment for locally advanced disease) * Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology) * Measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ function * Can provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable. * Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer * Female participants of childbearing potential should have a negative pregnancy test and must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication * Male participants must agree to use an adequate method of contraception starting with the first dose of study medication through 180 days after the last dose of study medication
Exclusion criteria
* Disease suitable for local therapy administered with curative intent * Has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC * Radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or not fully recovered from adverse events due to a previously administered treatment * Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of study medication * Life expectancy of \<3 months and/or has rapidly progressing disease * Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication (physiologic doses of corticosteroids may be approved after consultation with the Sponsor) * Diagnosed and/or treated additional malignancy within 5 years prior to randomization with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers * Has had an allogeneic tissue/solid organ transplant * Active central nervous system metastases and/or carcinomatous meningitis * Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment * History of (non-infectious) pneumonitis that required steroids or current pneumonitis * Active infection requiring systemic therapy * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial * Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study medication * Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or previously participated in Merck MK-3475 clinical trial * Known history of human immunodeficiency virus (HIV) * Known active Hepatitis B or C * Received a live vaccine within 30 days of planned start of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants | Up to approximately 47 months | PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 | Up to approximately 47 months | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as Combined Positive Score ≥1 (hereafter referred to as CPS ≥1). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | Up to approximately 47 months | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as Combined Positive Score ≥20 (hereafter referred to as CPS ≥20). Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Overall Survival (OS) in All Participants | Up to approximately 47 months | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, OS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1 | Up to approximately 47 months | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20 | Up to approximately 47 months | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants | Up to approximately 47 months | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | Up to approximately 47 months | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | Up to approximately 47 months | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: OS in All Participants | Up to approximately 47 months | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, OS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1 | Up to approximately 47 months | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20 | Up to approximately 47 months | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method) | Baseline up to approximately 12 months | EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score, for the first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro mono arm and control arm and is presented later in the record. |
| Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants | Month 6 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | Month 6 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | Month 6 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants | Month 12 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | Month 12 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | Month 12 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants | Up to approximately 47 months | ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants | Month 6 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | Up to approximately 47 months | ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | Baseline, Week 15 | The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score, for the first course of treatment, was compared between all participants of the pembro mono arm and the control arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | Baseline up to approximately 12 months | EORTC-QLQ-C30 is a 30-item questionnaire to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score | Baseline up to approximately 12 months | EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score | Baseline up to approximately 12 months | EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record. |
| Number of Participants Experiencing an Adverse Event (AE) | Up to approximately 47 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE, for the first course of treatment, was reported for each arm. |
| Number of Participants Who Discontinued Study Drug Due to an AE | Up to approximately 47 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued study drug due to an AE, for the first course of treatment, was reported for each arm. |
| Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | Up to approximately 47 months | ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. |
| Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | Month 6 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | Up to approximately 47 months | ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | Month 6 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants | Month 12 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | Month 12 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | Month 12 | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants | Up to approximately 47 months | ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | Up to approximately 47 months | ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score | Baseline, Week 15 | The EORTC-QLQ-C30 is a 30-item questionnaire to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score, for the first course of treatment, was compared between all participants of the pembro combo arm and the control arm as a pre-specified secondary analysis. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method) | Baseline up to approximately 12 months | EORTC-QLQ-C30 is a 30-item questionnaire to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score, for first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis; and TTD in GHS/QoL combined score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record. |
| Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method) | Baseline up to approximately 12 months | EORTC QLQ-H&N35 is a 35-item questionnaire to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score, for the first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record. |
Participant flow
Recruitment details
Participants with first line recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were recruited to examine the efficacy and safety of pembrolizumab monotherapy (pembro mono) versus pembrolizumab plus chemotherapy (pembro combo) versus cetuximab plus chemotherapy (control).
Pre-assignment details
Of 1228 participants screened, 882 were randomized to the pembro mono arm, pembro combo arm, or control arm. 22 participants in the control arm that enrolled during an enrollment pause of the pembro combo arm were excluded from efficacy comparisons between the pembro combo arm and control arm. Per protocol, response/progression or adverse events (AEs) that occurred during the second pembrolizumab course were not counted towards efficacy outcome measures or safety outcome measures, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 35 cycles (up to \
2 years). Qualified participants who received the first course of pembrolizumab but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule of 200 mg IV on Day 1 of each 3-week cycle for up to 17 cycles (up to \
1 year). | 301 |
| Pembrolizumab + Chemotherapy (Pembro Combo) Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 35 cycles (up to \
2 years); plus cisplatin 100 mg/m\^2 IV or carboplatin at a target area under the curve of 5 (AUC 5) IV, per Investigator's choice, on Day 1 of each 3-week cycle (6 cycle maximum \[up to \
4 months\]); plus 5-Fluorouracil (5-FU) 1000 mg/m\^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum \[up to \
4 months\]). Qualified participants who received the first course of pembrolizumab but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule of 200 mg IV on Day 1 of each 3-week cycle for up to 17 cycles (up to \
1 year). | 281 |
| Cetuximab + Chemotherapy (Control) Participants received cetuximab on Day 1 at a dose of 400 mg/m\^2 IV, and then 250 mg/m\^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity; plus cisplatin 100 mg/m\^2 IV or carboplatin AUC 5 IV (Investigator's choice) on Day 1 of each 3-week cycle (6 cycle maximum \[up to \
4 months\] for platinum-based therapy); plus 5-FU 1000 mg/m\^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum \[up to \
4 months\]). | 300 |
| Total | 882 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 253 | 237 | 266 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Sponsor Decision | 26 | 28 | 16 |
| Overall Study | Withdrawal by Subject | 19 | 14 | 18 |
Baseline characteristics
| Characteristic | Pembrolizumab Monotherapy (Pembro Mono) | Pembrolizumab + Chemotherapy (Pembro Combo) | Cetuximab + Chemotherapy (Control) | Total |
|---|---|---|---|---|
| Age, Continuous | 61.2 Years STANDARD_DEVIATION 9.4 | 60.7 Years STANDARD_DEVIATION 9.8 | 61.0 Years STANDARD_DEVIATION 10 | 61.0 Years STANDARD_DEVIATION 9.7 |
| Eastern Cooperative Group (ECOG) Performance Status ECOG = 0 | 118 Participants | 110 Participants | 117 Participants | 345 Participants |
| Eastern Cooperative Group (ECOG) Performance Status ECOG = 1 | 183 Participants | 171 Participants | 183 Participants | 537 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 45 Participants | 44 Participants | 135 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 233 Participants | 213 Participants | 231 Participants | 677 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 22 Participants | 23 Participants | 25 Participants | 70 Participants |
| Human Papillomavirus (HPV) Status HPV Negative | 238 Participants | 221 Participants | 233 Participants | 692 Participants |
| Human Papillomavirus (HPV) Status HPV Positive | 63 Participants | 60 Participants | 67 Participants | 190 Participants |
| PD-L1 CPS ≥1 Status CPS<1 | 44 Participants | 39 Participants | 45 Participants | 128 Participants |
| PD-L1 CPS ≥1 Status CPS ≥1 | 257 Participants | 242 Participants | 255 Participants | 754 Participants |
| PD-L1 CPS ≥20 Status CPS <20 | 167 Participants | 154 Participants | 175 Participants | 496 Participants |
| PD-L1 CPS ≥20 Status CPS ≥20 | 133 Participants | 126 Participants | 122 Participants | 381 Participants |
| PD-L1 CPS ≥20 Status Missing | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| PD-L1 TPS Status Not Strongly Positive | 234 Participants | 215 Participants | 234 Participants | 683 Participants |
| PD-L1 TPS Status Strongly Positive | 67 Participants | 66 Participants | 66 Participants | 199 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 3 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) Asian | 58 Participants | 60 Participants | 54 Participants | 172 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 11 Participants | 6 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 12 Participants | 4 Participants | 9 Participants | 25 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 219 Participants | 203 Participants | 224 Participants | 646 Participants |
| Sex: Female, Male Female | 51 Participants | 57 Participants | 39 Participants | 147 Participants |
| Sex: Female, Male Male | 250 Participants | 224 Participants | 261 Participants | 735 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 260 / 301 | 242 / 281 | 282 / 300 | 5 / 8 | 5 / 6 |
| other Total, other adverse events | 265 / 300 | 266 / 276 | 278 / 287 | 6 / 8 | 6 / 6 |
| serious Total, serious adverse events | 123 / 300 | 165 / 276 | 142 / 287 | 1 / 8 | 2 / 6 |
Outcome results
Primary
Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥1 were analyzed. 20 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1 | 13.6 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1 | 10.4 Months |
Comparison: OS in CPS ≥1 participants of the pembro combo arm was compared to OS in CPS ≥1 participants of the control arm to address the twelfth primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.0000295% CI: [0.53, 0.8]Regression, Cox
Primary
Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥20 were analyzed. 12 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20 | 14.7 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20 | 11.0 Months |
Comparison: OS in CPS ≥20 participants of the pembro combo arm was compared to OS in CPS ≥20 participants of the control arm to address the eleventh primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG and HPV status.p-value: 0.0004495% CI: [0.45, 0.82]Regression, Cox
Primary
Pembro Combo vs Control: Overall Survival (OS) in All Participants
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, OS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro combo arm or control arm during active enrollment were analyzed. 22 participants in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Overall Survival (OS) in All Participants | 13.0 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Overall Survival (OS) in All Participants | 10.7 Months |
Comparison: OS in all participants of the pembro combo arm was compared to OS in all participants of the control arm to address the fourteenth primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.0002595% CI: [0.6, 0.87]Regression, Cox
Primary
Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as Combined Positive Score ≥20 (hereafter referred to as CPS ≥20). Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥20 were analyzed. 12 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 5.8 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 5.3 Months |
Comparison: PFS in CPS ≥20 participants of the pembro combo arm was compared to PFS in CPS ≥20 participants of the control arm to address the fourth primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG and HPV status.p-value: 0.0295195% CI: [0.58, 1.01]Regression, Cox
Primary
Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as Combined Positive Score ≥1 (hereafter referred to as CPS ≥1). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥1 were analyzed. 20 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 | 5.1 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 | 5.0 Months |
Comparison: PFS in CPS ≥1 participants of the pembro combo arm was compared to PFS in CPS ≥1 participants of the control arm to address the fifth primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.0369795% CI: [0.69, 1.02]Regression, Cox
Primary
Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro combo arm or control arm during active enrollment were analyzed. 22 participants in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants | 4.9 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants | 5.2 Months |
Comparison: PFS in all participants of the pembro combo arm was compared to PFS in all participants of the control arm to address the sixth primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.2121195% CI: [0.78, 1.11]Regression, Cox
Primary
Pembro Mono vs Control: OS in All Participants
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, OS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: OS in All Participants | 11.5 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: OS in All Participants | 10.7 Months |
Comparison: OS in all participants of the pembro mono arm was compared to OS in all participants of the control arm to address the tenth primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.0198595% CI: [0.7, 0.99]Regression, Cox
Primary
Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥1 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1 | 12.3 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1 | 10.3 Months |
Comparison: OS in CPS ≥1 participants of the pembro mono arm was compared to OS in CPS ≥1 participants of the control arm to address the eighth primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.0013395% CI: [0.61, 0.9]Regression, Cox
Primary
Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥20 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20 | 14.8 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20 | 10.7 Months |
Comparison: OS in CPS ≥20 participants of the pembro mono arm was compared to OS in CPS ≥20 participants of the control arm to address the seventh primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG and HPV status.p-value: 0.000195% CI: [0.44, 0.78]Regression, Cox
Primary
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants | 2.3 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants | 5.2 Months |
Comparison: PFS in all participants of the pembro mono arm was compared to PFS in all participants of the control arm to address the third primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.998395% CI: [1.09, 1.53]Regression, Cox
Primary
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥1 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | 3.2 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | 5.0 Months |
Comparison: PFS in CPS ≥1 participants of the pembro mono arm was compared to PFS in CPS ≥1 participants of the control arm to address the second primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, HPV status and PD-L1 status.p-value: 0.895895% CI: [0.94, 1.36]Regression, Cox
Primary
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥20 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 3.4 Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 5.3 Months |
Comparison: PFS in CPS ≥20 participants of the pembro mono arm was compared to PFS in CPS ≥20 participants of the control arm to address the first primary hypothesis. The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG and HPV status.p-value: 0.4679195% CI: [0.76, 1.29]Regression, Cox
Secondary
Number of Participants Experiencing an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE, for the first course of treatment, was reported for each arm.
Time frame: Up to approximately 47 months
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Number of Participants Experiencing an Adverse Event (AE) | 290 Participants |
| Pembrolizumab + Chemotherapy (Pembro Combo) | Number of Participants Experiencing an Adverse Event (AE) | 271 Participants |
| Cetuximab + Chemotherapy (Control) | Number of Participants Experiencing an Adverse Event (AE) | 286 Participants |
Secondary
Number of Participants Who Discontinued Study Drug Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued study drug due to an AE, for the first course of treatment, was reported for each arm.
Time frame: Up to approximately 47 months
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Number of Participants Who Discontinued Study Drug Due to an AE | 36 Participants |
| Pembrolizumab + Chemotherapy (Pembro Combo) | Number of Participants Who Discontinued Study Drug Due to an AE | 90 Participants |
| Cetuximab + Chemotherapy (Control) | Number of Participants Who Discontinued Study Drug Due to an AE | 79 Participants |
Secondary
Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
The EORTC-QLQ-C30 is a 30-item questionnaire to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score, for the first course of treatment, was compared between all participants of the pembro combo arm and the control arm as a pre-specified secondary analysis. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Baseline, Week 15
Population: Participants in pembro combo arm and control arm who received ≥1 dose of study drug and with EORTC-QLQ-C30 assessments available at baseline or post-baseline up to Week 15. 20 in control arm enrolled during enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm compared to control arm separately and not included here.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score | 1.17 Score on a Scale |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score | 0.77 Score on a Scale |
Comparison: Change from baseline to Week 15 in EORTC-QLQ-C30 GHS/QoL combined score was compared between all participants of the pembro combo arm and the control arm. Comparison based on constrained longitudinal data analysis (cLDA) model with GHS/QoL score as response variable and treatment by visit interaction, stratification factors (ECOG \[0 vs. 1\], HPV status \[Positive vs. Negative\] and PD-L1 TPS status \[Strongly Positive, Not Strongly Positive\]) as covariates.p-value: 0.83995% CI: [-3.46, 4.26]constrained Longitudinal Data Analysis
Secondary
Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants
ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro combo arm or control arm during active enrollment were analyzed. 22 participants in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants | 35.6 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants | 36.3 Percentage of Participants |
Comparison: ORR in all participants of the pembro combo arm was compared to ORR in all participants of the control arm. The comparison was based on Miettinen \& Nurminen method stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.57495% CI: [-8.7, 7.2]Miettinen & Nurminen method
Secondary
Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥1 were analyzed. 20 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | 36.4 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | 35.7 Percentage of Participants |
Comparison: ORR in CPS ≥1 participants of the pembro combo arm was compared to ORR in CPS ≥1 participants of the control arm. The comparison was based on Miettinen \& Nurminen method stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.458695% CI: [-8.2, 9.1]Miettinen & Nurminen method
Secondary
Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Up to approximately 47 months
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥20 were analyzed. 12 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 42.9 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 38.2 Percentage of Participants |
Comparison: ORR in CPS ≥20 participants of the pembro combo arm was compared to ORR in CPS ≥20 participants of the control arm. The comparison was based on Miettinen \& Nurminen method stratified by ECOG (0 vs. 1) and HPV status (Positive vs. Negative).p-value: 0.216195% CI: [-7.5, 17.4]Miettinen & Nurminen method
Secondary
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Month 12
Population: All participants in the ITT population randomized to either the pembro combo arm or control arm during active enrollment were analyzed. 22 participants in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants | 17.2 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants | 13.6 Percentage of Participants |
Secondary
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Month 12
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥1 were analyzed. 20 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 19.7 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 12.5 Percentage of Participants |
Secondary
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Month 12
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥20 were analyzed. 12 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 23.9 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 14.0 Percentage of Participants |
Secondary
Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Month 6
Population: All participants in the ITT population randomized to either the pembro combo arm or control arm during active enrollment were analyzed. 22 participants in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants | 44.7 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants | 44.9 Percentage of Participants |
Secondary
Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Month 6
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥1 were analyzed. 20 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 44.9 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 43.3 Percentage of Participants |
Secondary
Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Time frame: Month 6
Population: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥20 were analyzed. 12 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 49.4 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 47.2 Percentage of Participants |
Secondary
Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method)
EORTC-QLQ-C30 is a 30-item questionnaire to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score, for first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis; and TTD in GHS/QoL combined score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record.
Time frame: Baseline up to approximately 12 months
Population: All participants in the pembro combo arm and the control arm who completed the EORTC QLQ-C30 and had received ≥1 dose of study drug. 20 in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, the pembro mono arm was compared to the control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method) | NA Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method) | NA Months |
Comparison: TTD in GHS/QoL combined score was compared between all participants of the pembro combo arm and the control arm. Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.949795% CI: [0.94, 2]Regression, Cox
Secondary
Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method)
EORTC QLQ-H&N35 is a 35-item questionnaire to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score, for the first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record.
Time frame: Baseline up to approximately 12 months
Population: All participants in the pembro combo arm and control arm who completed the EORTC QLQ-H\&N35 and had received ≥1 dose of study drug. 20 in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, the pembro mono arm was compared to the control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method) | NA Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method) | NA Months |
Comparison: TTD in EORTC QLQ-H\&N35 Pain Score was compared between all participants of the pembro combo arm and the control arm. Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.947695% CI: [0.93, 2.02]Regression, Cox
Secondary
Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method)
EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score, for the first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro mono arm and control arm and is presented later in the record.
Time frame: Baseline up to approximately 12 months
Population: All participants in the pembro combo arm and control arm who completed the EORTC QLQ-H\&N35 and had received ≥1 dose of study drug. 20 in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, the pembro mono arm was compared to the control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Chemotherapy (Pembro Combo) | Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method) | NA Months |
| Cetuximab + Chemotherapy (Control) | Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method) | NA Months |
Comparison: TTD in EORTC QLQ-H\&N35 Swallowing Score was compared between all participants of the pembro combo arm and the control arm. Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.583695% CI: [0.69, 1.59]Regression, Cox
Secondary
Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score, for the first course of treatment, was compared between all participants of the pembro mono arm and the control arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Baseline, Week 15
Population: All participants in the pembro mono arm and the control arm who received ≥1 dose of study drug and had EORTC-QLQ-C30 assessments available at baseline or post-baseline up to Week 15. Per protocol, the pembro combo arm was compared to the control arm separately and not included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | 0.85 Score on a Scale |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | 0.60 Score on a Scale |
Comparison: Change from baseline to Week 15 in EORTC-QLQ-C30 GHS/QoL combined score was compared between all participants of the pembro mono arm and the control arm. Comparison based on cLDA model with GHS/QoL score as response variable and treatment by visit interaction, stratification factors (ECOG \[0 vs. 1\], HPV status \[Positive vs. Negative\] and PD-L1 TPS status \[Strongly Positive, Not Strongly Positive\]) as covariates.p-value: 0.89395% CI: [-3.34, 3.82]constrained Longitudinal Data Analysis
Secondary
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants | 16.9 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants | 36.0 Percentage of Participants |
Comparison: ORR in all participants of the pembro mono arm was compared to ORR in all participants of the control arm. The comparison was based on Miettinen \& Nurminen method stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive , Not Strongly Positive).p-value: 195% CI: [-25.8, -12.1]Miettinen & Nurminen method
Secondary
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥1 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | 19.1 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 | 34.9 Percentage of Participants |
Comparison: ORR in CPS ≥1 participants of the pembro mono arm was compared to ORR in CPS ≥1 participants of the control arm. The comparison was based on Miettinen \& Nurminen method stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 195% CI: [-23.4, -8.3]Miettinen & Nurminen method
Secondary
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Up to approximately 47 months
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥20 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 23.3 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20 | 36.1 Percentage of Participants |
Comparison: ORR in CPS ≥20 participants of the pembro mono arm was compared to ORR in CPS ≥20 participants of the control arm. The comparison was based on Miettinen \& Nurminen method stratified by ECOG (0 vs. 1) and HPV status (Positive vs. Negative).p-value: 0.986995% CI: [-23.8, -1.5]Miettinen & Nurminen method
Secondary
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Month 12
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants | 17.6 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants | 15.0 Percentage of Participants |
Secondary
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Month 12
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥1 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 20.6 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 13.6 Percentage of Participants |
Secondary
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Month 12
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥20 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 23.5 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 15.1 Percentage of Participants |
Secondary
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Month 6
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants | 26.2 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants | 45.7 Percentage of Participants |
Secondary
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Month 6
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥1 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 28.7 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1 | 43.9 Percentage of Participants |
Secondary
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Time frame: Month 6
Population: All participants in the ITT population randomized to either the pembro mono arm or control arm during active enrollment with CPS ≥20 were analyzed. Per protocol, pembro combo arm was compared to control arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 33.0 Percentage of Participants |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20 | 46.6 Percentage of Participants |
Secondary
Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
EORTC-QLQ-C30 is a 30-item questionnaire to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record.
Time frame: Baseline up to approximately 12 months
Population: All participants in the pembro mono arm and the control arm who completed the EORTC QLQ-C30 and had received ≥1 dose of study drug. Per protocol, the pembro combo arm was compared to the control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | NA Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | NA Months |
Comparison: TTD in GHS/QoL combined score was compared between all participants of the pembro mono arm and the control arm. Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.95395% CI: [0.95, 2]Regression, Cox
Secondary
Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score
EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record.
Time frame: Baseline up to approximately 12 months
Population: All participants in the pembro mono arm and control arm who completed the EORTC QLQ-H\&N35 and had received ≥1 dose of study drug. Per protocol, the pembro combo arm was compared to the control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score | NA Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score | NA Months |
Comparison: TTD in EORTC QLQ-H\&N35 Pain Score was compared between all participants of the pembro mono arm and the control arm. Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.150195% CI: [0.53, 1.21]Regression, Cox
Secondary
Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score
EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record.
Time frame: Baseline up to approximately 12 months
Population: All participants in the pembro mono arm and control arm who completed the EORTC QLQ-H\&N35 and had received ≥1 dose of study drug. Per protocol, the pembro combo arm was compared to the control arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score | NA Months |
| Cetuximab + Chemotherapy (Control) | Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score | NA Months |
Comparison: TTD in EORTC QLQ-H\&N35 Swallowing Score was compared between all participants of the pembro mono arm and the control arm. Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG (0 vs. 1), HPV status (Positive vs. Negative) and PD-L1 TPS status (Strongly Positive, Not Strongly Positive).p-value: 0.875195% CI: [0.85, 1.88]Regression, Cox