Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck
Conditions
Keywords
Head and neck cancer; SCCHN
Brief summary
The purpose of this study is to determine the efficacy and safety of investigational medical products (MEDI4736 monotherapy, tremelimumab monotherapy, and MEDI4736 + tremelimumab combination therapy) in the treatment of patients with recurrent or metastatic carcinoma of the head and neck who have progressed during or after treatment with a platinum containing regimen for recurrent/metastatic disease.
Detailed description
This is a randomized, open-label, multi-center, global, Phase II study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy and tremelimumab monotherapy in the treatment of patients with recurrent or metastatic PD-L1-negative squamous cell carcinoma of the head and neck (SCCHN) who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease, that must have contained a platinum agent. Patients will be randomized in a stratified manner according to prognostic factors, including human papillomavirus (HPV) status and smoking status to achieve a balance between treatments for each of the factors. Patients will be randomized in a 1:1:2 fashion to receive MEDI4736 monotherapy, tremelimumab monotherapy, or MEDI4736 + tremelimumab combination. All treatments will be administered beginning on Day 0 for 12 months or until confirmed progression of disease; unless, in the Investigator's opinion, the patient continues to receive benefit from the treatment), initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. Patients with confirmed progression of disease who, in the Investigator's opinion, continue to receive benefit from their assigned investigational product and who meet the criteria for treatment in the setting of progression of disease may continue to receive their assigned investigational product treatment for a maximum of 12 months after consultation with the Sponsor and at the Investigator's discretion. The monotherapy arms (tremelimumab and MEDI4736) should be discontinued if there is confirmed progression of disease following a previous response in target lesions (complete response or partial response). Tumor assessments will be performed using computed tomography or magnetic resonance imaging. Efficacy for all patients will be assessed by objective tumor assessments every 8 weeks (q8w) for the first 48 weeks (relative to the date of the first infusion) then q12w in patients who have disease control after 12 months until confirmed objective disease progression. Following completion or discontinuation of treatment, patients will enter a follow-up period.
Interventions
DRUGMEDI4736
MEDI4736 monotherapy
DRUGTremelimumab
Tremelimumab monotherapy
MEDI4736 + Tremelimumab combination therapy
Sponsors
PRA Health Sciences
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 confirmed recurrent or metastatic SCCHN; tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent; Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible. * Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status. * Confirmed PD-L1-negative SCCHN by Ventana SP263; * WHO/ECOG performance status of 0 or 1; * At least 1 measurable lesion at baseline; * No prior exposure to immune-mediated therapy; * Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test.
Exclusion criteria
* Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck; * Received more than 1 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; * another primary malignancy * Patients with history of brain metastases, spinal cord compression, or a history of leptomeningeal carcinomatosis; * History of active primary immunodeficiency; * Known history of previous 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; * Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction * Known allergy or hypersensitivity to Investigational Product. * Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate at 6 Months | After 6 months | Objective response rate, primary analysis, based on BICR assessments according to RECIST v1.1. The number (%) of patients with a response excludes unconfirmed responses |
| Objective Response Rate at 12 Months | After 12 months | Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Objective Response | After 12 months | The best response a patient has had during their time in the study |
| Duration of Response - Participants Remaining in Response | After 12 months | Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off. |
| Time to Response | After 12 months | Time to response in patients with objective response based on BICR assessments according to RECIST 1.1 |
| Time to Onset of Response From First Dose | After 12 months | Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1 |
| Disease Control Rate (DCR) | After 6 months | Disease control rate (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization. |
| Progression-free Survival (PFS) | After 6 months | Progression status at 6 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression. |
| Overall Survival | After 12 months | Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status or patients who were lost to follow-up. |
| Quality of Life | After 12 months | Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: -The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3. -Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H&N35. The symptom and QoL/function improvement rate was defined as the number (%) of patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10 or EORTC QLQ-C30 scales) in that symptom/function from baseline. For QLQ-H&N35A a minimum clinically meaningful change was defined as a change in the score from baseline of \>10 for scales/items |
| Duration of Response | After 12 months | Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of Complete response/Partial response (which was subsequently confirmed) until the date of progression, death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off (per RECIST v1.1 as assessed by BICR). |
Countries
Australia, Belgium, Canada, Czechia, France, Georgia, Germany, Hungary, Israel, Malaysia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
127 sites in 15 countries enrolled and screened patients. The study was conducted and managed by PRA, a contract research organization.
Participants by arm
| Arm | Count |
|---|---|
| MEDI4736 + Tremelimumab MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment | 133 |
| MEDI4736 MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 67 |
| Tremelimumab Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses) | 67 |
| Total | 267 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 17 | 2 | 8 |
| Overall Study | Condition under investigation worsened | 100 | 50 | 46 |
| Overall Study | Death, PI/sponsor decision, med history | 0 | 1 | 4 |
| Overall Study | Not treated | 0 | 2 | 2 |
| Overall Study | Study specific discontinuation criteria | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 6 |
Baseline characteristics
| Characteristic | MEDI4736 + Tremelimumab | Total | Tremelimumab | MEDI4736 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 45 Participants | 91 Participants | 25 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants | 176 Participants | 42 Participants | 46 Participants |
| Age, Continuous | 62 years | 61 years | 61 years | 62 years |
| HPV status Negative | 94 Participants | 192 Participants | 49 Participants | 49 Participants |
| HPV status Positive | 39 Participants | 75 Participants | 18 Participants | 18 Participants |
| Negative PD-L1 status PD-L1 negative patients | 133 Participants | 267 Participants | 67 Participants | 67 Participants |
| Race/Ethnicity, Customized Asian ethnic group - Asian (not Chinese/Japanese) | 3 Participants | 6 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian ethnic group - Chinese | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian ethnic group - Total | 4 Participants | 9 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnic group - Hispanic or Latino | 8 Participants | 15 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnic group - Not Hispanic or Latino | 119 Participants | 241 Participants | 58 Participants | 64 Participants |
| Race/Ethnicity, Customized Ethnic group - Total | 127 Participants | 256 Participants | 63 Participants | 66 Participants |
| Race/Ethnicity, Customized Unknown or not reported | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 9 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 | 8 Participants | 18 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) White | 115 Participants | 230 Participants | 57 Participants | 58 Participants |
| Sex: Female, Male Female | 20 Participants | 47 Participants | 14 Participants | 13 Participants |
| Sex: Female, Male Male | 113 Participants | 220 Participants | 53 Participants | 54 Participants |
| Smoking/nicotine status by nicotine user Current smoker <= 10 pack years | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Smoking/nicotine status by nicotine user Current smoker >10 pack years | 22 Participants | 35 Participants | 6 Participants | 7 Participants |
| Smoking/nicotine status by nicotine user Former smoker <= 10 pack years | 30 Participants | 58 Participants | 12 Participants | 16 Participants |
| Smoking/nicotine status by nicotine user Former smoker >10 pack years | 59 Participants | 128 Participants | 34 Participants | 35 Participants |
| Smoking/nicotine status by nicotine user Never | 20 Participants | 43 Participants | 14 Participants | 9 Participants |
| Use of nicotine (other than cigarettes) No | 132 Participants | 265 Participants | 67 Participants | 66 Participants |
| Use of nicotine (other than cigarettes) Yes | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| WHO/ECOG performance status at study entry (0) Normal activity | 40 Participants | 81 Participants | 19 Participants | 22 Participants |
| WHO/ECOG performance status at study entry (1) Restricted activity | 93 Participants | 186 Participants | 48 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 86 / 133 | 44 / 67 | 51 / 67 |
| other Total, other adverse events | 110 / 133 | 52 / 65 | 59 / 65 |
| serious Total, serious adverse events | 59 / 133 | 18 / 65 | 25 / 65 |
Outcome results
Primary
Objective Response Rate at 12 Months
Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.
Time frame: After 12 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Overall | 7.8 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Current smoking/nicotine status - Total | 13.6 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Current smoking/nicotine status - >10 pack years | 15.0 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Current smoking/nicotine status - ≤10 pack years | 0 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Former smoking/nicotine status -Total | 6.8 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Former smoking/nicotine status - >10 pack years | 5.2 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Former smoking/nicotine status - ≤10 pack years | 10.0 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | Smoking/nicotine status - Never | 5.3 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | HPV status - Positive | 5.4 % participants |
| MEDI4736 + Tremelimumab | Objective Response Rate at 12 Months | HPV status - Negative | 8.7 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | Overall | 9.2 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | Former smoking/nicotine status - >10 pack years | 9.1 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | Former smoking/nicotine status -Total | 8.2 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | Current smoking/nicotine status - Total | 14.3 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | HPV status - Negative | 6.4 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | Smoking/nicotine status - Never | 11.1 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | Current smoking/nicotine status - >10 pack years | 14.3 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | Former smoking/nicotine status - ≤10 pack years | 6.3 % participants |
| MEDI4736 | Objective Response Rate at 12 Months | HPV status - Positive | 16.7 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Current smoking/nicotine status - ≤10 pack years | 0 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Smoking/nicotine status - Never | 0 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Former smoking/nicotine status -Total | 0 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Former smoking/nicotine status - >10 pack years | 0 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | HPV status - Positive | 0 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Former smoking/nicotine status - ≤10 pack years | 0 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Overall | 1.6 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | HPV status - Negative | 2.2 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Current smoking/nicotine status - Total | 14.3 % participants |
| Tremelimumab | Objective Response Rate at 12 Months | Current smoking/nicotine status - >10 pack years | 16.7 % participants |
Primary
Objective Response Rate at 6 Months
Objective response rate, primary analysis, based on BICR assessments according to RECIST v1.1. The number (%) of patients with a response excludes unconfirmed responses
Time frame: After 6 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI4736 + Tremelimumab | Objective Response Rate at 6 Months | 7.7 % participants |
| MEDI4736 | Objective Response Rate at 6 Months | 9.2 % participants |
| Tremelimumab | Objective Response Rate at 6 Months | 1.6 % participants |
Secondary
Best Objective Response
The best response a patient has had during their time in the study
Time frame: After 12 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Stable disease | 3.9 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Not evaluable-Incomplete post baseline tests | 2.3 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Progression | 64.3 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Progression-RECIST 1.1 progression | 45.7 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | Response - Total | 7.8 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | Response - Complete response (CR) | 0 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Progression-Death | 18.6 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | Non-response (NR) - Total | 92.2 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Not evaluable-SD <6 months (24 weeks) | 20.2 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Stable disease (SD) >=6 months (24 weeks) | 5.4 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Not evaluable-Total | 22.5 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | NR - Unconfirmed complete or partial response (PR) | 1.6 % participants |
| MEDI4736 + Tremelimumab | Best Objective Response | Response - Partial response (PR) | 7.8 % participants |
| MEDI4736 | Best Objective Response | NR - Stable disease | 6.2 % participants |
| MEDI4736 | Best Objective Response | Non-response (NR) - Total | 90.8 % participants |
| MEDI4736 | Best Objective Response | NR - Not evaluable-Incomplete post baseline tests | 3.1 % participants |
| MEDI4736 | Best Objective Response | Response - Complete response (CR) | 0 % participants |
| MEDI4736 | Best Objective Response | NR - Progression | 64.6 % participants |
| MEDI4736 | Best Objective Response | Response - Partial response (PR) | 9.2 % participants |
| MEDI4736 | Best Objective Response | NR - Not evaluable-Total | 20.0 % participants |
| MEDI4736 | Best Objective Response | Response - Total | 9.2 % participants |
| MEDI4736 | Best Objective Response | NR - Progression-RECIST 1.1 progression | 46.2 % participants |
| MEDI4736 | Best Objective Response | NR - Unconfirmed complete or partial response (PR) | 0 % participants |
| MEDI4736 | Best Objective Response | NR - Stable disease (SD) >=6 months (24 weeks) | 6.2 % participants |
| MEDI4736 | Best Objective Response | NR - Not evaluable-SD <6 months (24 weeks) | 16.9 % participants |
| MEDI4736 | Best Objective Response | NR - Progression-Death | 18.5 % participants |
| Tremelimumab | Best Objective Response | NR - Stable disease (SD) >=6 months (24 weeks) | 0 % participants |
| Tremelimumab | Best Objective Response | NR - Not evaluable-Total | 28.6 % participants |
| Tremelimumab | Best Objective Response | NR - Not evaluable-SD <6 months (24 weeks) | 19.0 % participants |
| Tremelimumab | Best Objective Response | Response - Partial response (PR) | 1.6 % participants |
| Tremelimumab | Best Objective Response | NR - Not evaluable-Incomplete post baseline tests | 9.5 % participants |
| Tremelimumab | Best Objective Response | Non-response (NR) - Total | 98.4 % participants |
| Tremelimumab | Best Objective Response | NR - Progression-Death | 15.9 % participants |
| Tremelimumab | Best Objective Response | Response - Total | 1.6 % participants |
| Tremelimumab | Best Objective Response | NR - Unconfirmed complete or partial response (PR) | 0 % participants |
| Tremelimumab | Best Objective Response | NR - Stable disease | 0 % participants |
| Tremelimumab | Best Objective Response | Response - Complete response (CR) | 0 % participants |
| Tremelimumab | Best Objective Response | NR - Progression | 69.8 % participants |
| Tremelimumab | Best Objective Response | NR - Progression-RECIST 1.1 progression | 54.0 % participants |
| Total | Best Objective Response | NR - Progression | 65.8 % participants |
| Total | Best Objective Response | Response - Total | 6.6 % participants |
| Total | Best Objective Response | Response - Complete response (CR) | 0 % participants |
| Total | Best Objective Response | Response - Partial response (PR) | 6.6 % participants |
| Total | Best Objective Response | Non-response (NR) - Total | 93.4 % participants |
| Total | Best Objective Response | NR - Stable disease (SD) >=6 months (24 weeks) | 4.3 % participants |
| Total | Best Objective Response | NR - Unconfirmed complete or partial response (PR) | 0.8 % participants |
| Total | Best Objective Response | NR - Stable disease | 3.5 % participants |
| Total | Best Objective Response | NR - Progression-RECIST 1.1 progression | 47.9 % participants |
| Total | Best Objective Response | NR - Progression-Death | 17.9 % participants |
| Total | Best Objective Response | NR - Not evaluable-Total | 23.3 % participants |
| Total | Best Objective Response | NR - Not evaluable-SD <6 months (24 weeks) | 19.1 % participants |
| Total | Best Objective Response | NR - Not evaluable-Incomplete post baseline tests | 4.3 % participants |
Secondary
Disease Control Rate (DCR)
Disease control rate (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.
Time frame: After 6 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | METHOD 1: Disease control (DC) at 6 months | 13.2 % participants |
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months | 86.8 % participants |
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months-Not evaluable/missing | 20.2 % participants |
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | METHOD 2: DC at 6 months | 20.2 % participants |
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months | 79.8 % participants |
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months-Not evaluable/missing | 20.2 % participants |
| MEDI4736 | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months-Not evaluable/missing | 20.0 % participants |
| MEDI4736 | Disease Control Rate (DCR) | METHOD 2: DC at 6 months | 26.2 % participants |
| MEDI4736 | Disease Control Rate (DCR) | METHOD 1: Disease control (DC) at 6 months | 21.5 % participants |
| MEDI4736 | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months-Not evaluable/missing | 20.0 % participants |
| MEDI4736 | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months | 78.5 % participants |
| MEDI4736 | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months | 73.8 % participants |
| Tremelimumab | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months | 98.4 % participants |
| Tremelimumab | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months-Not evaluable/missing | 22.2 % participants |
| Tremelimumab | Disease Control Rate (DCR) | METHOD 2: DC at 6 months | 9.5 % participants |
| Tremelimumab | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months-Not evaluable/missing | 22.2 % participants |
| Tremelimumab | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months | 90.5 % participants |
| Tremelimumab | Disease Control Rate (DCR) | METHOD 1: Disease control (DC) at 6 months | 1.6 % participants |
| Total | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months | 80.9 % participants |
| Total | Disease Control Rate (DCR) | METHOD 2: No DC at 6 months-Not evaluable/missing | 20.6 % participants |
| Total | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months | 87.5 % participants |
| Total | Disease Control Rate (DCR) | METHOD 2: DC at 6 months | 19.1 % participants |
| Total | Disease Control Rate (DCR) | METHOD 1: Disease control (DC) at 6 months | 12.5 % participants |
| Total | Disease Control Rate (DCR) | METHOD 1: No DC at 6 months-Not evaluable/missing | 20.6 % participants |
Secondary
Disease Control Rate (DCR)
Disease control rate (DCR) at 12 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.
Time frame: After 12 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | No DC at 12 months-Not evaluable/missing | 20.2 % participants |
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | DC at 12 months | 10.1 % participants |
| MEDI4736 + Tremelimumab | Disease Control Rate (DCR) | No DC at 12 months | 89.9 % participants |
| MEDI4736 | Disease Control Rate (DCR) | DC at 12 months | 12.3 % participants |
| MEDI4736 | Disease Control Rate (DCR) | No DC at 12 months-Not evaluable/missing | 20.0 % participants |
| MEDI4736 | Disease Control Rate (DCR) | No DC at 12 months | 87.7 % participants |
| Tremelimumab | Disease Control Rate (DCR) | No DC at 12 months | 98.4 % participants |
| Tremelimumab | Disease Control Rate (DCR) | DC at 12 months | 1.6 % participants |
| Tremelimumab | Disease Control Rate (DCR) | No DC at 12 months-Not evaluable/missing | 22.2 % participants |
| Total | Disease Control Rate (DCR) | DC at 12 months | 8.6 % participants |
| Total | Disease Control Rate (DCR) | No DC at 12 months-Not evaluable/missing | 20.6 % participants |
| Total | Disease Control Rate (DCR) | No DC at 12 months | 91.4 % participants |
Secondary
Duration of Response
Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of Complete response/Partial response (which was subsequently confirmed) until the date of progression, death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off (per RECIST v1.1 as assessed by BICR).
Time frame: After 12 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Duration of Response | No. progressed or died within 12 months | 5 Participants |
| MEDI4736 + Tremelimumab | Duration of Response | No. progressed or died after 12 months | 0 Participants |
| MEDI4736 | Duration of Response | No. progressed or died after 12 months | 0 Participants |
| MEDI4736 | Duration of Response | No. progressed or died within 12 months | 2 Participants |
| Tremelimumab | Duration of Response | No. progressed or died within 12 months | 0 Participants |
| Tremelimumab | Duration of Response | No. progressed or died after 12 months | 0 Participants |
| Total | Duration of Response | No. progressed or died within 12 months | 7 Participants |
| Total | Duration of Response | No. progressed or died after 12 months | 0 Participants |
Secondary
Duration of Response - Participants Remaining in Response
Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Time frame: After 12 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-12 months | 46.7 % participants |
| MEDI4736 + Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-6 months | 70.0 % participants |
| MEDI4736 + Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage of ongoing response | 50.0 % participants |
| MEDI4736 + Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-9 months | 58.3 % participants |
| MEDI4736 + Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-3 months | 90.0 % participants |
| MEDI4736 | Duration of Response - Participants Remaining in Response | Percentage remaining in response-9 months | 66.7 % participants |
| MEDI4736 | Duration of Response - Participants Remaining in Response | Percentage remaining in response-12 months | NA % participants |
| MEDI4736 | Duration of Response - Participants Remaining in Response | Percentage of ongoing response | 66.7 % participants |
| MEDI4736 | Duration of Response - Participants Remaining in Response | Percentage remaining in response-6 months | 66.7 % participants |
| MEDI4736 | Duration of Response - Participants Remaining in Response | Percentage remaining in response-3 months | 100 % participants |
| Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-9 months | NA % participants |
| Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-3 months | 100 % participants |
| Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-6 months | 100 % participants |
| Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage remaining in response-12 months | NA % participants |
| Tremelimumab | Duration of Response - Participants Remaining in Response | Percentage of ongoing response | 100 % participants |
| Total | Duration of Response - Participants Remaining in Response | Percentage remaining in response-12 months | 53.5 % participants |
| Total | Duration of Response - Participants Remaining in Response | Percentage remaining in response-6 months | 70.6 % participants |
| Total | Duration of Response - Participants Remaining in Response | Percentage remaining in response-3 months | 94.1 % participants |
| Total | Duration of Response - Participants Remaining in Response | Percentage remaining in response-9 months | 64.2 % participants |
| Total | Duration of Response - Participants Remaining in Response | Percentage of ongoing response | 58.8 % participants |
Secondary
Overall Survival
Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status or patients who were lost to follow-up.
Time frame: After 12 months
Population: Full analysis set - all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Overall Survival | Terminated prior to death-Voluntary discon. | 5.3 % participants |
| MEDI4736 + Tremelimumab | Overall Survival | Still in survival follow-up | 30.1 % participants |
| MEDI4736 + Tremelimumab | Overall Survival | Terminated prior to death-Other | 0 % participants |
| MEDI4736 + Tremelimumab | Overall Survival | Terminated prior to death | 5.3 % participants |
| MEDI4736 + Tremelimumab | Overall Survival | Death | 64.7 % participants |
| MEDI4736 | Overall Survival | Terminated prior to death | 6.0 % participants |
| MEDI4736 | Overall Survival | Terminated prior to death-Voluntary discon. | 6.0 % participants |
| MEDI4736 | Overall Survival | Terminated prior to death-Other | 0 % participants |
| MEDI4736 | Overall Survival | Still in survival follow-up | 28.4 % participants |
| MEDI4736 | Overall Survival | Death | 65.7 % participants |
| Tremelimumab | Overall Survival | Terminated prior to death | 7.5 % participants |
| Tremelimumab | Overall Survival | Death | 76.1 % participants |
| Tremelimumab | Overall Survival | Still in survival follow-up | 16.4 % participants |
| Tremelimumab | Overall Survival | Terminated prior to death-Voluntary discon. | 4.5 % participants |
| Tremelimumab | Overall Survival | Terminated prior to death-Other | 3.0 % participants |
| Total | Overall Survival | Terminated prior to death-Voluntary discon. | 5.2 % participants |
| Total | Overall Survival | Still in survival follow-up | 26.2 % participants |
| Total | Overall Survival | Death | 67.8 % participants |
| Total | Overall Survival | Terminated prior to death | 6.0 % participants |
| Total | Overall Survival | Terminated prior to death-Other | 0.7 % participants |
Secondary
Progression-free Survival (PFS)
Progression status at 6 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.
Time frame: After 6 months
Population: Full analysis set - all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-Withdrawn consent | 0.8 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression- Discontinued study | 0 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-PD free and still being followed | 14.3 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | Progression-Total | 82.0 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-Censored on Study Day 1 | 1.5 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 43.6 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 21.1 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 57.9 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression- Censored death | 1.5 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 26.3 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | Progression-Death | 24.1 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-Total | 18.0 % participants |
| MEDI4736 | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 59.7 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-Total | 17.9 % participants |
| MEDI4736 | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 26.9 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-Censored on Study Day 1 | 0 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-Withdrawn consent | 3.0 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-PD free and still being followed | 13.4 % participants |
| MEDI4736 | Progression-free Survival (PFS) | Progression-Total | 82.1 % participants |
| MEDI4736 | Progression-free Survival (PFS) | Progression-Death | 22.4 % participants |
| MEDI4736 | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 20.9 % participants |
| MEDI4736 | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 43.3 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression- Discontinued study | 0 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression- Censored death | 1.5 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-PD free and still being followed | 4.5 % participants |
| Tremelimumab | Progression-free Survival (PFS) | Progression-Total | 88.1 % participants |
| Tremelimumab | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 67.2 % participants |
| Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 55.2 % participants |
| Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 32.8 % participants |
| Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 26.9 % participants |
| Tremelimumab | Progression-free Survival (PFS) | Progression-Death | 20.9 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-Total | 11.9 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-Censored on Study Day 1 | 0 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-Withdrawn consent | 1.5 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression- Censored death | 3.0 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression- Discontinued study | 3.0 % participants |
| Total | Progression-free Survival (PFS) | Progression-Death | 22.8 % participants |
| Total | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 25.1 % participants |
| Total | Progression-free Survival (PFS) | Progression-Total | 83.5 % participants |
| Total | Progression-free Survival (PFS) | No progression-Withdrawn consent | 1.5 % participants |
| Total | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 25.5 % participants |
| Total | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 46.4 % participants |
| Total | Progression-free Survival (PFS) | No progression- Discontinued study | 0.7 % participants |
| Total | Progression-free Survival (PFS) | No progression- Censored death | 1.9 % participants |
| Total | Progression-free Survival (PFS) | No progression-PD free and still being followed | 11.6 % participants |
| Total | Progression-free Survival (PFS) | No progression-Total | 16.5 % participants |
| Total | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 60.7 % participants |
| Total | Progression-free Survival (PFS) | No progression-Censored on Study Day 1 | 0.7 % participants |
Secondary
Progression-free Survival (PFS)
Progression status at 12 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.
Time frame: After 12 months
Population: Full analysis set - all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | Progression-Total | 88.7 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 23.3 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-PD free and still being followed | 6.8 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 64.7 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-Total | 11.3 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 27.1 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 50.4 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-Discontinued study | 0 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-Withdrawn consent | 0.8 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | Progression-Death | 24.1 % participants |
| MEDI4736 + Tremelimumab | Progression-free Survival (PFS) | No progression-Censored death | 3.8 % participants |
| MEDI4736 | Progression-free Survival (PFS) | Progression-Death | 23.9 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-Censored death | 0 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-Total | 16.4 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-PD free and still being followed | 11.9 % participants |
| MEDI4736 | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 47.8 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-Discontinued study | 0 % participants |
| MEDI4736 | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 28.4 % participants |
| MEDI4736 | Progression-free Survival (PFS) | No progression-Withdrawn consent | 4.5 % participants |
| MEDI4736 | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 23.9 % participants |
| MEDI4736 | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 59.7 % participants |
| MEDI4736 | Progression-free Survival (PFS) | Progression-Total | 83.6 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-Withdrawn consent | 1.5 % participants |
| Tremelimumab | Progression-free Survival (PFS) | Progression-Total | 89.6 % participants |
| Tremelimumab | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 68.7 % participants |
| Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 56.7 % participants |
| Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 32.8 % participants |
| Tremelimumab | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 23.9 % participants |
| Tremelimumab | Progression-free Survival (PFS) | Progression-Death | 20.9 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-Total | 10.4 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-PD free and still being followed | 3.0 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-Censored death | 3.0 % participants |
| Tremelimumab | Progression-free Survival (PFS) | No progression-Discontinued study | 3.0 % participants |
| Total | Progression-free Survival (PFS) | Progression-Death | 23.2 % participants |
| Total | Progression-free Survival (PFS) | No progression-Discontinued study | 0.7 % participants |
| Total | Progression-free Survival (PFS) | No progression-Censored death | 2.6 % participants |
| Total | Progression-free Survival (PFS) | RECIST 1.1 progression-New lesions | 25.5 % participants |
| Total | Progression-free Survival (PFS) | RECIST 1.1 progression-Non-target lesions | 27.0 % participants |
| Total | Progression-free Survival (PFS) | RECIST 1.1 progression-Target Lesions | 51.3 % participants |
| Total | Progression-free Survival (PFS) | No progression-Withdrawn consent | 1.9 % participants |
| Total | Progression-free Survival (PFS) | Total-RECIST 1.1 Progression | 64.4 % participants |
| Total | Progression-free Survival (PFS) | Progression-Total | 87.6 % participants |
| Total | Progression-free Survival (PFS) | No progression-PD free and still being followed | 7.1 % participants |
| Total | Progression-free Survival (PFS) | No progression-Total | 12.4 % participants |
Secondary
Quality of Life
Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: -The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3. -Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H&N35. The symptom and QoL/function improvement rate was defined as the number (%) of patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10 or EORTC QLQ-C30 scales) in that symptom/function from baseline. For QLQ-H&N35A a minimum clinically meaningful change was defined as a change in the score from baseline of \>10 for scales/items
Time frame: After 12 months
Population: Full analysis set - all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Pain | 16.7 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Swallowing | 16.0 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Senses | 17.8 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Speech | 20.2 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Social contact | 22.6 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Social eating | 21.3 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Sexuality | 16.2 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Physical | 12 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Role | 16.3 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Cognitive | 25 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Emotional | 13.5 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Social | 18.3 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Symptom-Fatigue | 16.8 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Symptom-Pain | 22.8 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Symptom-Nausea/vomiting | 22.2 % patients |
| MEDI4736 + Tremelimumab | Quality of Life | EORTC QLQ-C30 Global health status/QoL | 13.4 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Function-Social | 15.2 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-H&N35 Scale-Sexuality | 9.5 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Symptom-Fatigue | 17.3 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Function-Physical | 13.6 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Function-Role | 16.7 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Symptom-Nausea/vomiting | 16.7 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Function-Cognitive | 29.4 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Symptom-Pain | 20.8 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-H&N35 Scale-Pain | 19.4 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Function-Emotional | 13.6 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-H&N35 Scale-Swallowing | 13.3 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-C30 Global health status/QoL | 7.3 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-H&N35 Scale-Senses | 24.3 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-H&N35 Scale-Speech | 9.8 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-H&N35 Scale-Social eating | 20.0 % patients |
| MEDI4736 | Quality of Life | EORTC QLQ-H&N35 Scale-Social contact | 5.9 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Symptom-Pain | 6.7 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Social contact | 13.0 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Speech | 19.6 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Social | 16.1 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Global health status/QoL | 3.7 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Symptom-Nausea/vomiting | 17.6 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Sexuality | 9.5 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Pain | 8.3 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Social eating | 15.0 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Physical | 5.1 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Symptom-Fatigue | 7.5 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Senses | 23.1 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Role | 11.8 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-H&N35 Scale-Swallowing | 10.3 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Emotional | 2.6 % patients |
| Tremelimumab | Quality of Life | EORTC QLQ-C30 Function-Cognitive | 10.7 % patients |
Secondary
Time to Onset of Response From First Dose
Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1
Time frame: After 12 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI4736 + Tremelimumab | Time to Onset of Response From First Dose | 2.0 Months |
| MEDI4736 | Time to Onset of Response From First Dose | 4.1 Months |
| Tremelimumab | Time to Onset of Response From First Dose | 1.8 Months |
| Total | Time to Onset of Response From First Dose | 3.5 Months |
Secondary
Time to Response
Time to response in patients with objective response based on BICR assessments according to RECIST 1.1
Time frame: After 12 months
Population: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI4736 + Tremelimumab | Time to Response | Week 25, where response is first observed | 10.0 % participants |
| MEDI4736 + Tremelimumab | Time to Response | Week 16, where response is first observed | 10.0 % participants |
| MEDI4736 + Tremelimumab | Time to Response | Number of responders | 100 % participants |
| MEDI4736 + Tremelimumab | Time to Response | Week 9, where response is first observed | 50.0 % participants |
| MEDI4736 + Tremelimumab | Time to Response | Week 24, where response is first observed | 10.0 % participants |
| MEDI4736 + Tremelimumab | Time to Response | Week 20, where response is first observed | 0 % participants |
| MEDI4736 + Tremelimumab | Time to Response | Week 17, where response is first observed | 10.0 % participants |
| MEDI4736 + Tremelimumab | Time to Response | Week 8, where response is first observed | 10.0 % participants |
| MEDI4736 | Time to Response | Week 9, where response is first observed | 16.7 % participants |
| MEDI4736 | Time to Response | Week 24, where response is first observed | 16.7 % participants |
| MEDI4736 | Time to Response | Week 25, where response is first observed | 16.7 % participants |
| MEDI4736 | Time to Response | Week 16, where response is first observed | 16.7 % participants |
| MEDI4736 | Time to Response | Week 8, where response is first observed | 0 % participants |
| MEDI4736 | Time to Response | Number of responders | 100 % participants |
| MEDI4736 | Time to Response | Week 17, where response is first observed | 16.7 % participants |
| MEDI4736 | Time to Response | Week 20, where response is first observed | 16.7 % participants |
| Tremelimumab | Time to Response | Week 16, where response is first observed | 0 % participants |
| Tremelimumab | Time to Response | Week 25, where response is first observed | 0 % participants |
| Tremelimumab | Time to Response | Week 20, where response is first observed | 0 % participants |
| Tremelimumab | Time to Response | Number of responders | 100 % participants |
| Tremelimumab | Time to Response | Week 24, where response is first observed | 0 % participants |
| Tremelimumab | Time to Response | Week 9, where response is first observed | 100 % participants |
| Tremelimumab | Time to Response | Week 17, where response is first observed | 0 % participants |
| Tremelimumab | Time to Response | Week 8, where response is first observed | 0 % participants |
| Total | Time to Response | Week 25, where response is first observed | 11.8 % participants |
| Total | Time to Response | Number of responders | 100 % participants |
| Total | Time to Response | Week 8, where response is first observed | 5.9 % participants |
| Total | Time to Response | Week 9, where response is first observed | 41.2 % participants |
| Total | Time to Response | Week 16, where response is first observed | 11.8 % participants |
| Total | Time to Response | Week 17, where response is first observed | 11.8 % participants |
| Total | Time to Response | Week 20, where response is first observed | 5.9 % participants |
| Total | Time to Response | Week 24, where response is first observed | 11.8 % participants |