Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHN
Conditions
Keywords
Head and Neck cancer; MEDI4736; Tremelimumab
Brief summary
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.
Detailed description
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population. The main objectives of the study are to: * assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in patients with squamous cell carcinoma of the head and neck (SCCHN), in terms of overall survival (OS), regardless of PDL-1 status * assess the efficacy of MEDI4736 monotherapy versus SOC in patients with SCCHN, in terms of OS, regardless of PDL-1 status Patients will undergo a screening assessment on their tumor tissue sample to determine PD-L1 expression per a pre-specified cut-off level. Patients with ≥25% of tumor cells with membrane staining will be considered PD-L1 positive while those with 0% to 24% of tumor cells with membrane staining will be considered PD-L1 negative. Based on the underlying PD-L1 status, patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 monotherapy, MEDI4736 + tremelimumab combination therapy, or SoC therapy. Patients who discontinue treatment in 1 treatment group may not switch to treatment in a different group. Stratification factors include PD-L1 status, human papillomavirus status, (in patients with oropharyngeal cancer only), and smoking status. Tumor assessments will be performed every 8 weeks until objective tumor response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Interventions
DRUGMEDI4736
MEDI4736 Monotherapy
MEDI4736 + Tremelimumab combination therapy
DRUGStandard of Care
Standard of Care
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 96 Years
Healthy volunteers
No
Inclusion criteria
- Age ≥18 years; - Written informed consent obtained from the patient/legal representative; - Histologically or cytologically confirmed recurrent or metastatic SCCHN; - Tumor progression or recurrence during or after only one palliative systemic treatment regimen for recurrent or metastatic disease that must have contained a platinum agent OR progression within 6 months of the last dose of platinum given as part of multimodality therapy with curative intent; - Confirmed PD-L1-positive or -negative SCCHN by the Ventana PD-L1 SP263 IHC assay; - WHO/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; At least 1 measurable lesion, - Not previously irradiated; - No prior exposure to immune-mediated therapy; - Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
Exclusion criteria
- Histologically or cytologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck; - Received more than 1 palliative systemic regimen for recurrent or metastatic disease; -Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment; - Receipt of any investigational anticancer therapy within 28 days or 5 half-lives; - Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment; - Major surgical procedure within 28 days prior to the first dose of Investigational Product; - Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion; - Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned Investigational Product; - History of allogeneic organ transplantation; - Active or prior documented autoimmune or inflammatory disorders; - Uncontrolled intercurrent illness; - Patients with a history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis; - Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction; - History of active primary immunodeficiency; - Active tuberculosis; - Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV); - Receipt of live, attenuated vaccine within 30 days prior to the first dose of Investigational Product; - Pregnant or breast-feeding female patients; - Known allergy or hypersensitivity to Investigational Product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | September 2015 to September 2018 (36 months) | OS is defined as the time from the date of randomization until death due to any cause. OS was analyzed for the full analysis set, regardless of programmed death-ligand 1 (PD-L1) status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in PD-L1 Positive Participants | September 2015 to September 2018 (36 months) | OS is defined as the time from the date of randomization until death due to any cause. PD-L1 positive was defined as ≥25% of tumor cells with membrane staining for PD-L1 at any intensity. |
| Progression Free Survival (PFS) | September 2015 to September 2018 (36 months) | PFS was defined as the time from the date of randomization until the date of objective disease progression or death based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Objective Response Rate (ORR) | Assessed at randomization and every 8 weeks thereafter | The percentage of participants who experienced an objective response (complete response \[CR\] or partial response \[PR\]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. |
| Duration of Response (DoR) | September 2015 to September 2018 (36 months) | Median DoR, in months, based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A complete response was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A partial response was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. |
| Disease Control Rate (DCR) | Baseline up to 6 months; baseline up to 12 months | 6 Months: The percentage of participants who had a best objective response of complete response (CR) or partial response (PR) in the first 6 months or had demonstrated stable disease (SD) for a minimum interval of 24 weeks following randomization. 12 Months: The percentage of participants who had a best objective response of CR or PR within 12 months or had demonstrated SD for a minimum interval of 48 weeks following randomization. Objective response was based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. |
| Percentage of Participants Alive and Progression Free (APF) | Baseline up to 6 months; baseline up to 12 months | APF is defined as the percentage of participants who are alive and progression free at 6 months and 12 months after randomization. Estimates of progression free survival were based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Overall Survival (OS) in PD-L1 Negative Participants | September 2015 to September 2018 (36 months) | OS is defined as the time from the date of randomization until death due to any cause. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity. |
| Progression Free Survival (PFS) in PD-L1 Negative Participants | September 2015 to September 2018 (36 months) | Number of participants with confirmed objective disease progression (PD) at the time of the participant's last evaluable response evaluation criteria in solid tumors 1.1 (RECIST1.1) assessment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity. |
| Objective Response Rate (ORR) in PD-L1 Negative Participants | September 2015 to September 2018 (36 months) | The percentage of PD-L1 negative participants who experienced an objective response (complete response \[CR\] or partial response \[PR\]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity. |
| Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | September 2015 to September 2018 (36 months) | The EORTC QLQ-C30 consists of 30 questions that can be combined to produce functional scales (e.g. physical), symptom scales (e.g. fatigue), and a global measure of health status. Each of the scales are measured from 0 to 100. Deterioration was defined as a 10-point decrease from baseline in a functioning or global health status/ quality of life score or a 10-point increase from baseline in a symptom score. |
| Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) | September 2015 to September 2018 (36 months) | The EORTC QLQ-H&N35 comprises of 35 questions to assess head and neck cancer symptoms (e.g. pain, swallowing). Deterioration was defined as a 10-point increase from baseline in the symptom score. |
| Number of Participants Reporting One or More Adverse Events (AE) | First dose to last dose + 90 days or data cut off (up to 36 months) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Inclusive of AEs and serious AEs. |
| Percentage of Participants Alive | 12, 18 and 24 months | Percentage of participants alive at 12, 18 and 24 months using a Kaplan Meier estimate. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Croatia, Czechia, France, Georgia, Germany, Hungary, Israel, Italy, Japan, Poland, Romania, Russia, Serbia, South Korea, Spain, Taiwan, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab + Tremelimumab Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD). | 247 |
| Durvalumab Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD). | 240 |
| Standard of Care (SoC) Participants received monotherapy with 1 of the following therapies at the investigator's discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine. | 249 |
| Total | 736 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 | 2 |
| Overall Study | Miscellaneous | 1 | 1 | 0 |
| Overall Study | On Treatment/Off Study | 34 | 45 | 32 |
| Overall Study | Withdrawal by Subject | 7 | 9 | 27 |
Baseline characteristics
| Characteristic | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SoC) | Total |
|---|---|---|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 9.14 | 59.0 Years STANDARD_DEVIATION 10.07 | 59.5 Years STANDARD_DEVIATION 10.37 | 59.4 Years STANDARD_DEVIATION 9.86 |
| Age, Customized >= 65 - < 75 Years | 63 Participants | 56 Participants | 64 Participants | 183 Participants |
| Age, Customized < 65 Years | 174 Participants | 169 Participants | 171 Participants | 514 Participants |
| Age, Customized >= 75 Years | 10 Participants | 15 Participants | 14 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 15 Participants | 13 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 226 Participants | 223 Participants | 229 Participants | 678 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 7 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 33 Participants | 35 Participants | 45 Participants | 113 Participants |
| Race/Ethnicity, Customized Black Or African American | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 5 Participants | 3 Participants | 12 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 5 Participants | 2 Participants | 9 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 204 Participants | 198 Participants | 189 Participants | 591 Participants |
| Sex: Female, Male Female | 38 Participants | 38 Participants | 42 Participants | 118 Participants |
| Sex: Female, Male Male | 209 Participants | 202 Participants | 207 Participants | 618 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 206 / 247 | 186 / 240 | 199 / 249 |
| other Total, other adverse events | 203 / 246 | 180 / 237 | 207 / 240 |
| serious Total, serious adverse events | 79 / 246 | 69 / 237 | 61 / 240 |
Outcome results
Primary
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause. OS was analyzed for the full analysis set, regardless of programmed death-ligand 1 (PD-L1) status.
Time frame: September 2015 to September 2018 (36 months)
Population: Full analysis set - inclusive of all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) | 6.5 Months |
| Durvalumab | Overall Survival (OS) | 7.6 Months |
| Standard of Care (SoC) | Overall Survival (OS) | 8.3 Months |
p-value: 0.762495% CI: [0.85, 1.26]Log Rank
p-value: 0.199395% CI: [0.72, 1.08]Log Rank
Secondary
Disease Control Rate (DCR)
6 Months: The percentage of participants who had a best objective response of complete response (CR) or partial response (PR) in the first 6 months or had demonstrated stable disease (SD) for a minimum interval of 24 weeks following randomization. 12 Months: The percentage of participants who had a best objective response of CR or PR within 12 months or had demonstrated SD for a minimum interval of 48 weeks following randomization. Objective response was based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Time frame: Baseline up to 6 months; baseline up to 12 months
Population: Full analysis set - inclusive of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Disease Control Rate (DCR) | 6 Months | 25.1 Percentage of participants |
| Durvalumab + Tremelimumab | Disease Control Rate (DCR) | 12 Months | 20.6 Percentage of participants |
| Durvalumab | Disease Control Rate (DCR) | 6 Months | 24.2 Percentage of participants |
| Durvalumab | Disease Control Rate (DCR) | 12 Months | 18.8 Percentage of participants |
| Standard of Care (SoC) | Disease Control Rate (DCR) | 6 Months | 24.9 Percentage of participants |
| Standard of Care (SoC) | Disease Control Rate (DCR) | 12 Months | 18.9 Percentage of participants |
Comparison: 6 Month analysis95% CI: [0.67, 1.52]
Comparison: 6 Month analysis95% CI: [0.64, 1.46]
Comparison: 12 Month analysis95% CI: [0.72, 1.75]
Comparison: 12 Month analysis95% CI: [0.63, 1.57]
Secondary
Duration of Response (DoR)
Median DoR, in months, based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A complete response was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A partial response was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Time frame: September 2015 to September 2018 (36 months)
Population: Full analysis set, participants with objective response - inclusive of all randomized participants with an objective response (RECIST 1.1).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Duration of Response (DoR) | 7.4 Months |
| Durvalumab | Duration of Response (DoR) | 12.9 Months |
| Standard of Care (SoC) | Duration of Response (DoR) | 3.7 Months |
Secondary
Number of Participants Reporting One or More Adverse Events (AE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Inclusive of AEs and serious AEs.
Time frame: First dose to last dose + 90 days or data cut off (up to 36 months)
Population: Safety analysis set - inclusive of all participants that received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab + Tremelimumab | Number of Participants Reporting One or More Adverse Events (AE) | 232 Participants |
| Durvalumab | Number of Participants Reporting One or More Adverse Events (AE) | 214 Participants |
| Standard of Care (SoC) | Number of Participants Reporting One or More Adverse Events (AE) | 229 Participants |
Secondary
Objective Response Rate (ORR)
The percentage of participants who experienced an objective response (complete response \[CR\] or partial response \[PR\]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Time frame: Assessed at randomization and every 8 weeks thereafter
Population: Full analysis set - inclusive of all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab + Tremelimumab | Objective Response Rate (ORR) | 18.2 Percentage of participants |
| Durvalumab | Objective Response Rate (ORR) | 17.9 Percentage of participants |
| Standard of Care (SoC) | Objective Response Rate (ORR) | 17.3 Percentage of participants |
95% CI: [0.67, 1.7]
95% CI: [0.66, 1.68]
Secondary
Objective Response Rate (ORR) in PD-L1 Negative Participants
The percentage of PD-L1 negative participants who experienced an objective response (complete response \[CR\] or partial response \[PR\]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time frame: September 2015 to September 2018 (36 months)
Population: PD-L1-negative analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-negative as defined by the Ventana PD-L1 SP263 IHC assay.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab + Tremelimumab | Objective Response Rate (ORR) in PD-L1 Negative Participants | 17.7 Percentage of participants |
| Durvalumab | Objective Response Rate (ORR) in PD-L1 Negative Participants | 14.0 Percentage of participants |
| Standard of Care (SoC) | Objective Response Rate (ORR) in PD-L1 Negative Participants | 15.3 Percentage of participants |
95% CI: [0.74, 2.39]
Secondary
Overall Survival (OS) in PD-L1 Negative Participants
OS is defined as the time from the date of randomization until death due to any cause. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time frame: September 2015 to September 2018 (36 months)
Population: PD-L1-negative analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-negative as defined by the Ventana PD-L1 SP263 IHC assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) in PD-L1 Negative Participants | 7.8 Months |
| Durvalumab | Overall Survival (OS) in PD-L1 Negative Participants | 7.6 Months |
| Standard of Care (SoC) | Overall Survival (OS) in PD-L1 Negative Participants | 8.0 Months |
p-value: 0.45995% CI: [0.73, 1.17]Log Rank
95% CI: [0.85, 1.36]
Secondary
Overall Survival (OS) in PD-L1 Positive Participants
OS is defined as the time from the date of randomization until death due to any cause. PD-L1 positive was defined as ≥25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time frame: September 2015 to September 2018 (36 months)
Population: PD-L1-positive analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-positive as defined by the Ventana PD-L1 SP263 IHC assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) in PD-L1 Positive Participants | 4.8 Months |
| Durvalumab | Overall Survival (OS) in PD-L1 Positive Participants | 9.8 Months |
| Standard of Care (SoC) | Overall Survival (OS) in PD-L1 Positive Participants | 9.0 Months |
95% CI: [0.63, 1.39]
Secondary
Percentage of Participants Alive
Percentage of participants alive at 12, 18 and 24 months using a Kaplan Meier estimate.
Time frame: 12, 18 and 24 months
Population: Full analysis set - inclusive of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Percentage of Participants Alive | 18 Months | 21.0 Percentage of participants |
| Durvalumab + Tremelimumab | Percentage of Participants Alive | 12 Months | 30.4 Percentage of participants |
| Durvalumab + Tremelimumab | Percentage of Participants Alive | 24 Months | 13.3 Percentage of participants |
| Durvalumab | Percentage of Participants Alive | 18 Months | 25.4 Percentage of participants |
| Durvalumab | Percentage of Participants Alive | 12 Months | 37.0 Percentage of participants |
| Durvalumab | Percentage of Participants Alive | 24 Months | 18.4 Percentage of participants |
| Standard of Care (SoC) | Percentage of Participants Alive | 12 Months | 30.5 Percentage of participants |
| Standard of Care (SoC) | Percentage of Participants Alive | 24 Months | 10.3 Percentage of participants |
| Standard of Care (SoC) | Percentage of Participants Alive | 18 Months | 17.8 Percentage of participants |
Secondary
Percentage of Participants Alive and Progression Free (APF)
APF is defined as the percentage of participants who are alive and progression free at 6 months and 12 months after randomization. Estimates of progression free survival were based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Baseline up to 6 months; baseline up to 12 months
Population: Full analysis set - inclusive of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Percentage of Participants Alive and Progression Free (APF) | 6 Months | 22.5 Percentage of participants |
| Durvalumab + Tremelimumab | Percentage of Participants Alive and Progression Free (APF) | 12 Months | 11.0 Percentage of participants |
| Durvalumab | Percentage of Participants Alive and Progression Free (APF) | 6 Months | 25.1 Percentage of participants |
| Durvalumab | Percentage of Participants Alive and Progression Free (APF) | 12 Months | 14.4 Percentage of participants |
| Standard of Care (SoC) | Percentage of Participants Alive and Progression Free (APF) | 6 Months | 23.3 Percentage of participants |
| Standard of Care (SoC) | Percentage of Participants Alive and Progression Free (APF) | 12 Months | 5.7 Percentage of participants |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization until the date of objective disease progression or death based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: September 2015 to September 2018 (36 months)
Population: Full analysis set - inclusive of all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Progression Free Survival (PFS) | 2.0 Months |
| Durvalumab | Progression Free Survival (PFS) | 2.1 Months |
| Standard of Care (SoC) | Progression Free Survival (PFS) | 3.7 Months |
95% CI: [0.9, 1.33]
95% CI: [0.84, 1.25]
Secondary
Progression Free Survival (PFS) in PD-L1 Negative Participants
Number of participants with confirmed objective disease progression (PD) at the time of the participant's last evaluable response evaluation criteria in solid tumors 1.1 (RECIST1.1) assessment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time frame: September 2015 to September 2018 (36 months)
Population: PD-L1-negative analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-negative as defined by the Ventana PD-L1 SP263 IHC assay.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab + Tremelimumab | Progression Free Survival (PFS) in PD-L1 Negative Participants | 154 Participants |
| Durvalumab | Progression Free Survival (PFS) in PD-L1 Negative Participants | 151 Participants |
| Standard of Care (SoC) | Progression Free Survival (PFS) in PD-L1 Negative Participants | 144 Participants |
95% CI: [0.76, 1.21]
Secondary
Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35)
The EORTC QLQ-H&N35 comprises of 35 questions to assess head and neck cancer symptoms (e.g. pain, swallowing). Deterioration was defined as a 10-point increase from baseline in the symptom score.
Time frame: September 2015 to September 2018 (36 months)
Population: All randomized patients who provided questionnaire data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) | Pain (Mouth/ Throat) | 2.9 Months |
| Durvalumab + Tremelimumab | Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) | Swallowing | 2.6 Months |
| Durvalumab | Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) | Pain (Mouth/ Throat) | 2.8 Months |
| Durvalumab | Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) | Swallowing | 2.8 Months |
| Standard of Care (SoC) | Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) | Pain (Mouth/ Throat) | 3.4 Months |
| Standard of Care (SoC) | Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) | Swallowing | 3.7 Months |
Secondary
Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30)
The EORTC QLQ-C30 consists of 30 questions that can be combined to produce functional scales (e.g. physical), symptom scales (e.g. fatigue), and a global measure of health status. Each of the scales are measured from 0 to 100. Deterioration was defined as a 10-point decrease from baseline in a functioning or global health status/ quality of life score or a 10-point increase from baseline in a symptom score.
Time frame: September 2015 to September 2018 (36 months)
Population: All randomized patients who provided questionnaire data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Symptom - Fatigue | 1.8 Months |
| Durvalumab + Tremelimumab | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Function - Physical | 2.0 Months |
| Durvalumab + Tremelimumab | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Global health status/QoL | 1.9 Months |
| Durvalumab | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Symptom - Fatigue | 1.4 Months |
| Durvalumab | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Function - Physical | 2.2 Months |
| Durvalumab | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Global health status/QoL | 2.8 Months |
| Standard of Care (SoC) | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Function - Physical | 3.7 Months |
| Standard of Care (SoC) | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Global health status/QoL | 3.5 Months |
| Standard of Care (SoC) | Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) | Symptom - Fatigue | 1.9 Months |