Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Brief summary
The goal of this study is to evaluate the efficacy and safety of pembrolizumab combined with carboplatin and paclitaxel as first-line treatment in participants with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). No statistical hypothesis will be tested in this study.
Interventions
DRUGPembrolizumab
Pembrolizumab 200 mg IV infusion given on Day 1 of each 21-day cycle
DRUGCarboplatin
Carboplatin AUC 5 mg/mL/minute IV infusion given on Day 1 of each 21-day cycle
DRUGPaclitaxel
At investigator's choice, paclitaxel 100 mg/m\^2 IV infusion given on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m\^2 IV infusion given on Day 1 of each 21-day cycle
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically or cytologically-confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies * Male participants refrain from donating sperm plus are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 95 days after carboplatin/paclitaxel * Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) or use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after pembrolizumab or 30 days after paclitaxel or 6 months after carboplatin whichever occurs last, and agree not to donate or freeze eggs during this period * Has adequate organ function
Exclusion criteria
* Has disease that is suitable for local therapy administered with curative intent * Has a life expectancy of less than 3 months and/or has rapidly progressive disease * Has a diagnosed and/or treated additional malignancy within 5 years prior to allocation with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively resected in situ cervical cancer and curatively resected in situ breast cancer * Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has a history of or current non-infectious pneumonitis/interstitial lung disease that requires steroids * Has an active infection requiring systemic therapy * Has a known history of human immunodeficiency virus (HIV) infection * Has a known history of Hepatitis B or Hepatitis C virus infection * Has had an allogenic tissue/solid organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to ~25 months | ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per Response Evaluation Criteria in Solid Tumors Update and Clarification 1.1 (RECIST 1.1) which was adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR as assessed by blinded independent central review based on RECIST 1.1 was presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to ~25 months | For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurred first. RECIST 1.1 was adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR as assessed by blinded independent central review based on RECIST 1.1 was presented. |
| Progression-free Survival (PFS) | Up to ~25 months | PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. RECIST 1.1 was been adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by blinded independent central review based on RECIST 1.1 was from product-limit (Kaplan-Meier) method for censored data. |
| Overall Survival (OS) | Up to ~25 months | OS was defined as the time from first dose of study treatment to death due to any cause. PFS as assessed by blinded independent central review based on RECIST 1.1 was from product-limit (Kaplan-Meier) method for censored data. |
| Percentage of Participants Who Experienced an Adverse Event (AE) | Up to ~39 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced an AE was reported. |
| Percentage of Participants Who Discontinued Study Treatment Due to an AE | Up to ~25 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study treatment due to an AE was reported. |
Countries
Argentina, Australia, Brazil, Canada, United States
Participant flow
Recruitment details
101 participants were enrolled in the All Participants as Treated (APaT) population. The APaT population consisted of all allocated participants who received at least one dose of study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + Carboplatin + Paclitaxel Participants received pembrolizumab plus carboplatin plus paclitaxel. Pembrolizumab was administered via intravenous (IV) infusion at a dose of 200 mg on Day 1 of each 21-day cycle for up to 35 cycles (up to \
2 years). Carboplatin was administered via IV infusion at area under curve (AUC) 5 mg/mL/minute on Day 1 of each 21-day cycle for up to 6 cycles (up to \
4 months). At investigator's choice, paclitaxel was administered via IV infusion at a dose of 100 mg/m\^2 on Day 1 and Day 8 of each 21-day cycle for up to 6 cycles (up to \
4 months) or at a dose of 175 mg/m\^2 on Day 1 of each 21-day cycle for up to 6 cycles (up to \
4 months). | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 75 |
| Overall Study | Sponsor Decision | 26 |
Baseline characteristics
| Characteristic | Pembrolizumab + Carboplatin + Paclitaxel |
|---|---|
| Age, Continuous | 63.8 Years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 88 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 75 / 101 |
| other Total, other adverse events | 100 / 101 |
| serious Total, serious adverse events | 52 / 101 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per Response Evaluation Criteria in Solid Tumors Update and Clarification 1.1 (RECIST 1.1) which was adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR as assessed by blinded independent central review based on RECIST 1.1 was presented.
Time frame: Up to ~25 months
Population: APaT population, which included all participants enrolled who received at least 1 dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Carboplatin + Paclitaxel | Objective Response Rate (ORR) | 48.5 Percentage of Participants |
Secondary
Duration of Response (DOR)
For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurred first. RECIST 1.1 was adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR as assessed by blinded independent central review based on RECIST 1.1 was presented.
Time frame: Up to ~25 months
Population: Participants in APaT population who had either a CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Carboplatin + Paclitaxel | Duration of Response (DOR) | 5.5 Months |
Secondary
Overall Survival (OS)
OS was defined as the time from first dose of study treatment to death due to any cause. PFS as assessed by blinded independent central review based on RECIST 1.1 was from product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~25 months
Population: APaT population, which included all participants enrolled who received at least 1 dose of study intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Carboplatin + Paclitaxel | Overall Survival (OS) | 13.1 Months |
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to an AE
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study treatment due to an AE was reported.
Time frame: Up to ~25 months
Population: APaT population, which included all participants enrolled who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Carboplatin + Paclitaxel | Percentage of Participants Who Discontinued Study Treatment Due to an AE | 36.6 Percentage of Participants |
Secondary
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced an AE was reported.
Time frame: Up to ~39 months
Population: APaT population, which included all participants enrolled who received at least 1 dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Carboplatin + Paclitaxel | Percentage of Participants Who Experienced an Adverse Event (AE) | 100.0 Percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. RECIST 1.1 was been adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by blinded independent central review based on RECIST 1.1 was from product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~25 months
Population: APaT population, which included all participants enrolled who received at least 1 dose of study intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Carboplatin + Paclitaxel | Progression-free Survival (PFS) | 5.6 Months |