Head and Neck Cancer
Conditions
Keywords
Head and neck squamous cell carcinoma, programmed cell death 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor
Brief summary
The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab + cisplatin or carboplatin + 5-fluorouracil) as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Interventions
DRUGPembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
DRUGEpacadostat
Epacadostat administered orally twice daily.
DRUGCetuximab
Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.
DRUGCisplatin
Cisplatin administered intravenously every 3 weeks for \</= 6 cycles.
DRUGCarboplatin
Carboplatin administered intravenously every 3 weeks for \</= 6 cycles.
DRUG5-Fluorouracil
5-Fluorouracil administered intravenously every 3 weeks for \</= 6 cycles.
Sponsors
Merck Sharp & Dohme LLC
Incyte Corporation
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
* Measurable disease based on RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function per protocol-defined criteria. * Documentation of results from testing of human papilloma virus (HPV) status for oropharyngeal cancer. * Baseline archival tumor specimen available or willing to undergo a prestudy treatment tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain the specimen.
Exclusion criteria
* Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors. * Disease progression within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC. * Use of protocol-defined prior/concomitant therapy. * Known additional malignancy that is progressing or has required active treatment within the past 3 years. * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Active autoimmune disease that has required systemic treatment in past 2 years. * Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority. * Known history of or is positive for active hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (defined as HCV RNA \[qualitative\] is detected).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen | Minimum Week 9 | ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination. Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs) | Up to 14 months | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months. |
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs | Up to 14 months | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months. |
Countries
Australia, Austria, Canada, Hungary, Italy, Japan, Poland, Portugal, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
This study was conducted at 76 centers in 14 countries.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + Epacadostat Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. | 35 |
| Pembrolizumab Pembrolizumab administered intravenously every 3 weeks. | 19 |
| EXTREME EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.
Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for \</= 6 cycles. Carboplatin administered intravenously every 3 weeks for \</= 6 cycles. 5-Fluorouracil administered intravenously every 3 weeks for \</= 6 cycles. | 35 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 6 | 3 | 10 |
| Overall Study | On-going at clinical cut off date | 9 | 6 | 5 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | EXTREME | Pembrolizumab | Pembrolizumab + Epacadostat |
|---|---|---|---|---|
| Age, Customized | 62.5 years STANDARD_DEVIATION 9.4 | 62.7 years STANDARD_DEVIATION 10 | 63.0 years STANDARD_DEVIATION 9.6 | 62.1 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 86 Participants | 35 Participants | 17 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Primary Tumor Site Hypopharynx | 16 Participants | 9 Participants | 3 Participants | 4 Participants |
| Primary Tumor Site Larynx | 21 Participants | 7 Participants | 5 Participants | 9 Participants |
| Primary Tumor Site Oral Cavity | 22 Participants | 7 Participants | 5 Participants | 10 Participants |
| Primary Tumor Site Oropharynx | 30 Participants | 12 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized Asian | 24 Participants | 13 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Black Or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 64 Participants | 22 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Female | 14 Participants | 6 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 75 Participants | 29 Participants | 16 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 35 | 4 / 19 | 10 / 35 |
| other Total, other adverse events | 34 / 34 | 17 / 19 | 34 / 34 |
| serious Total, serious adverse events | 12 / 34 | 8 / 19 | 12 / 34 |
Outcome results
Primary
Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen
ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination. Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans.
Time frame: Minimum Week 9
Population: The Intention-to-Treat (ITT) population consisted of all randomized participants.~The ORR was based on all available imaging assessments after the last participant completed the Week 9 imaging assessment by investigator determination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Epacadostat | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen | 31.4 percentage of participants |
| Pembrolizumab | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen | 21.1 percentage of participants |
| EXTREME | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen | 34.3 percentage of participants |
Secondary
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs
AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.
Time frame: Up to 14 months
Population: All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + Epacadostat | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs | 3 Participants |
| Pembrolizumab | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs | 2 Participants |
| EXTREME | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs | 7 Participants |
Secondary
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)
AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.
Time frame: Up to 14 months
Population: All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + Epacadostat | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs) | 34 Participants |
| Pembrolizumab | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs) | 17 Participants |
| EXTREME | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs) | 34 Participants |