Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in Combination w/ Tremelimumab Squamous Cell Carcinoma of the Head and Neck
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02319044
Collaborator
PRA Health Sciences (Industry)
267
125
3
62.7
2.1
0
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
267 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy, Tremelimumab Monotherapy, and MEDI4736 in Combination With Tremelimumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Actual Study Start Date
:
Apr 15, 2015
Actual Primary Completion Date
:
Sep 26, 2016
Actual Study Completion Date
:
Jul 6, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MEDI4736 MEDI4736 monotherapy |
Drug: MEDI4736
MEDI4736 monotherapy
|
| Experimental: Tremelimumab Tremelimumab monotherapy |
Drug: Tremelimumab
Tremelimumab monotherapy
|
| Experimental: MEDI4736 + Tremelimumab MEDI4736 + Tremelimumab combination therapy |
Drug: MEDI4736 + Tremelimumab
MEDI4736 + Tremelimumab combination therapy
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- Disease Control Rate (DCR) [After 12 months]
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.
- 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.
- Progression-free Survival (PFS) [After 12 months]
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.
- 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).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 96 Years
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Birmingham | Alabama | United States | 35294 |
| 2 | Research Site | Yuma | Arizona | United States | 85364 |
| 3 | Research Site | Little Rock | Arkansas | United States | 72205 |
| 4 | Research Site | Downey | California | United States | 90241 |
| 5 | Research Site | Duarte | California | United States | 91010-3012 |
| 6 | Research Site | La Jolla | California | United States | 92093 |
| 7 | Research Site | Long Beach | California | United States | 90813 |
| 8 | Research Site | Los Angeles | California | United States | 90033 |
| 9 | Research Site | Los Angeles | California | United States | 90095 |
| 10 | Research Site | San Francisco | California | United States | 94115 |
| 11 | Research Site | Aurora | Colorado | United States | 80045 |
| 12 | Research Site | Tampa | Florida | United States | 33612 |
| 13 | Research Site | Atlanta | Georgia | United States | 30322 |
| 14 | Research Site | Augusta | Georgia | United States | 30912 |
| 15 | Research Site | Macon | Georgia | United States | 31201 |
| 16 | Research Site | Chicago | Illinois | United States | 60637 |
| 17 | Research Site | Evanston | Illinois | United States | 60201 |
| 18 | Research Site | Lexington | Kentucky | United States | 40536-0001 |
| 19 | Research Site | Baltimore | Maryland | United States | 21201 |
| 20 | Research Site | Baltimore | Maryland | United States | 21204 |
| 21 | Research Site | Boston | Massachusetts | United States | 02215 |
| 22 | Research Site | Ann Arbor | Michigan | United States | 48109 |
| 23 | Research Site | Detroit | Michigan | United States | 48201 |
| 24 | Research Site | Southfield | Michigan | United States | 48075 |
| 25 | Research Site | Rochester | Minnesota | United States | 55905-0001 |
| 26 | Research Site | Saint Louis | Missouri | United States | 63110 |
| 27 | Research Site | Lebanon | New Hampshire | United States | 03756 |
| 28 | Research Site | Bronx | New York | United States | 10467 |
| 29 | Research Site | New York | New York | United States | 10032 |
| 30 | Research Site | Stony Brook | New York | United States | 11794 |
| 31 | Research Site | Durham | North Carolina | United States | 27705 |
| 32 | Research Site | Winston-Salem | North Carolina | United States | 27157 |
| 33 | Research Site | Portland | Oregon | United States | 97239 |
| 34 | Research Site | Bethlehem | Pennsylvania | United States | 18015 |
| 35 | Research Site | Pittsburgh | Pennsylvania | United States | 15232 |
| 36 | Research Site | Charleston | South Carolina | United States | 29425 |
| 37 | Research Site | Knoxville | Tennessee | United States | 37909 |
| 38 | Research Site | Nashville | Tennessee | United States | 37232 |
| 39 | Research Site | Arlington | Texas | United States | 76012 |
| 40 | Research Site | Austin | Texas | United States | 78701 |
| 41 | Research Site | Dallas | Texas | United States | 75230 |
| 42 | Research Site | Morgantown | West Virginia | United States | 26506 |
| 43 | Research Site | Milwaukee | Wisconsin | United States | 53226 |
| 44 | Research Site | Adelaide | Australia | 5000 | |
| 45 | Research Site | Darlinghurst | Australia | 2010 | |
| 46 | Research Site | Tweed Heads | Australia | 2485 | |
| 47 | Research Site | Brussels | Belgium | 1090 | |
| 48 | Research Site | Charleroi | Belgium | 6000 | |
| 49 | Research Site | Kortrijk | Belgium | 8500 | |
| 50 | Research Site | Leuven | Belgium | 3000 | |
| 51 | Research Site | Namur | Belgium | 5000 | |
| 52 | Research Site | Calgary | Alberta | Canada | T2N 2T9 |
| 53 | Research Site | Moncton | New Brunswick | Canada | E1C 6Z8 |
| 54 | Research Site | London | Ontario | Canada | N6A 4L6 |
| 55 | Research Site | Ottawa | Ontario | Canada | K1H 8L6 |
| 56 | Research Site | Toronto | Ontario | Canada | M5G 2M9 |
| 57 | Research Site | Montreal | Quebec | Canada | H4A 3J1 |
| 58 | Research Site | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 59 | Research Site | Olomouc | Czechia | 775 20 | |
| 60 | Research Site | Zlin | Czechia | 762 75 | |
| 61 | Research Site | Angers | France | 49933 | |
| 62 | Research Site | Bordeaux | France | 33604 | |
| 63 | Research Site | Brest | France | 29229 | |
| 64 | Research Site | Dijon | France | 21079 | |
| 65 | Research Site | Le Mans | France | 72000 | |
| 66 | Research Site | Lille cedex | France | 59020 | |
| 67 | Research Site | Lorient cedex | France | 56322 | |
| 68 | Research Site | Lyon Cedex 08 | France | 69373 | |
| 69 | Research Site | Montpellier | France | 34298 | |
| 70 | Research Site | Nice | France | 6189 | |
| 71 | Research Site | Rouen | France | 76038 | |
| 72 | Research Site | Saint Brieuc | France | 22015 | |
| 73 | Research Site | St Grégoire | France | 35768 | |
| 74 | Research Site | Strasbourg Cedex | France | 67085 | |
| 75 | Research Site | Toulouse Cedex 9 | France | 31059 | |
| 76 | Research Site | Villejuif Cedex | France | 94805 | |
| 77 | Research Site | Batumi | Georgia | 6010 | |
| 78 | Research Site | Batumi | Georgia | 6400 | |
| 79 | Research Site | Tbilisi | Georgia | 0144 | |
| 80 | Research Site | Tbilisi | Georgia | 0177 | |
| 81 | Research Site | Tbilisi | Georgia | 0179 | |
| 82 | Research Site | Berlin | Germany | 12203 | |
| 83 | Research Site | Halle | Germany | 06120 | |
| 84 | Research Site | Hannover | Germany | 30625 | |
| 85 | Research Site | Heidelberg | Germany | 69120 | |
| 86 | Research Site | Leipzig | Germany | 04103 | |
| 87 | Research Site | München | Germany | 81377 | |
| 88 | Research Site | Budapest | Hungary | 1077 | |
| 89 | Research Site | Budapest | Hungary | 1083 | |
| 90 | Research Site | Budapest | Hungary | 1122 | |
| 91 | Research Site | Gyula | Hungary | 5700 | |
| 92 | Research Site | Györ | Hungary | 9024 | |
| 93 | Research Site | Kecskemét | Hungary | 6000 | |
| 94 | Research Site | Miskolc | Hungary | 3526 | |
| 95 | Research Site | Zalaegerszeg | Hungary | 8900 | |
| 96 | Research Site | Haifa | Israel | 31096 | |
| 97 | Research Site | Petach-Tikva | Israel | 4941492 | |
| 98 | Research Site | Tel Hashomer | Israel | 52621 | |
| 99 | Research Site | Daegu | Korea, Republic of | 42601 | |
| 100 | Research Site | Goyang-si | Korea, Republic of | 10408 | |
| 101 | Research Site | Suwon | Korea, Republic of | 16247 | |
| 102 | Research Site | Kuala Lumpur | Malaysia | 59100 | |
| 103 | Research Site | Kuching | Malaysia | 93586 | |
| 104 | Research Site | Barakaldo | Spain | 48903 | |
| 105 | Research Site | Barcelona | Spain | 08035 | |
| 106 | Research Site | Barcelona | Spain | 08036 | |
| 107 | Research Site | Barcelona | Spain | 08907 | |
| 108 | Research Site | Gerona | Spain | 17007 | |
| 109 | Research Site | Granada | Spain | 18014 | |
| 110 | Research Site | Jaén | Spain | 23007 | |
| 111 | Research Site | Madrid | Spain | 28041 | |
| 112 | Research Site | Madrid | Spain | 28046 | |
| 113 | Research Site | Madrid | Spain | 28050 | |
| 114 | Research Site | Malaga | Spain | 29010 | |
| 115 | Research Site | Marbella (Málaga) | Spain | 29600 | |
| 116 | Research Site | Valencia | Spain | 46014 | |
| 117 | Research Site | Valencia | Spain | 46026 | |
| 118 | Research Site | Zaragoza | Spain | 50009 | |
| 119 | Research Site | Taipei | Taiwan | 10449 | |
| 120 | Research Site | Aberdeen | United Kingdom | AB25 2ZN | |
| 121 | Research Site | Birmingham | United Kingdom | B15 2TH | |
| 122 | Research Site | Glasgow | United Kingdom | G12 0YN | |
| 123 | Research Site | London | United Kingdom | E1 1BB | |
| 124 | Research Site | Manchester | United Kingdom | M20 4BX | |
| 125 | Research Site | Wirral | United Kingdom | CH63 4JY |
Sponsors and Collaborators
- AstraZeneca
- PRA Health Sciences
Investigators
- Study Director: Magdalena Wrona, Medical Scientist AstraZeneca Magdalena.Wrona@astrazeneca.com
- Principal Investigator: Lillian Siu, MD, Princess Margaret Hospital in Toronto, Ontario
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02319044
Other Study ID Numbers:
- D4193C00003
First Posted:
Dec 18, 2014
Last Update Posted:
Sep 29, 2020
Last Verified:
Sep 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MEDI4736 AND TREMELIMUMAB COMBINATION | MEDI4736 | Tremelimumab |
|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) |
| Period Title: Overall Study | |||
| STARTED | 133 | 67 | 67 |
| COMPLETED | 11 | 7 | 0 |
| NOT COMPLETED | 122 | 60 | 67 |
Baseline Characteristics
| Arm/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total of all reporting groups |
| Overall Participants | 133 | 67 | 67 | 267 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
88
66.2%
|
46
68.7%
|
42
62.7%
|
176
65.9%
|
| >=65 years |
45
33.8%
|
21
31.3%
|
25
37.3%
|
91
34.1%
|
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
62
|
62
|
61
|
61
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
20
15%
|
13
19.4%
|
14
20.9%
|
47
17.6%
|
| Male |
113
85%
|
54
80.6%
|
53
79.1%
|
220
82.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
4
3%
|
3
4.5%
|
2
3%
|
9
3.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
6
4.5%
|
3
4.5%
|
1
1.5%
|
10
3.7%
|
| White |
115
86.5%
|
58
86.6%
|
57
85.1%
|
230
86.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
8
6%
|
3
4.5%
|
7
10.4%
|
18
6.7%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Ethnic group - Hispanic or Latino |
8
6%
|
2
3%
|
5
7.5%
|
15
5.6%
|
| Ethnic group - Not Hispanic or Latino |
119
89.5%
|
64
95.5%
|
58
86.6%
|
241
90.3%
|
| Ethnic group - Total |
127
95.5%
|
66
98.5%
|
63
94%
|
256
95.9%
|
| Asian ethnic group - Asian (not Chinese/Japanese) |
3
2.3%
|
2
3%
|
1
1.5%
|
6
2.2%
|
| Asian ethnic group - Chinese |
1
0.8%
|
1
1.5%
|
1
1.5%
|
3
1.1%
|
| Asian ethnic group - Total |
4
3%
|
3
4.5%
|
2
3%
|
9
3.4%
|
| Unknown or not reported |
2
1.5%
|
0
0%
|
2
3%
|
4
1.5%
|
| Negative PD-L1 status (Count of Participants) | ||||
| PD-L1 negative patients |
133
100%
|
67
100%
|
67
100%
|
267
100%
|
| HPV status (Count of Participants) | ||||
| Positive |
39
29.3%
|
18
26.9%
|
18
26.9%
|
75
28.1%
|
| Negative |
94
70.7%
|
49
73.1%
|
49
73.1%
|
192
71.9%
|
| Use of nicotine (other than cigarettes) (Count of Participants) | ||||
| Yes |
1
0.8%
|
1
1.5%
|
0
0%
|
2
0.7%
|
| No |
132
99.2%
|
66
98.5%
|
67
100%
|
265
99.3%
|
| Smoking/nicotine status by nicotine user (Count of Participants) | ||||
| Current smoker >10 pack years |
22
16.5%
|
7
10.4%
|
6
9%
|
35
13.1%
|
| Current smoker <= 10 pack years |
2
1.5%
|
0
0%
|
1
1.5%
|
3
1.1%
|
| Former smoker >10 pack years |
59
44.4%
|
35
52.2%
|
34
50.7%
|
128
47.9%
|
| Former smoker <= 10 pack years |
30
22.6%
|
16
23.9%
|
12
17.9%
|
58
21.7%
|
| Never |
20
15%
|
9
13.4%
|
14
20.9%
|
43
16.1%
|
| WHO/ECOG performance status at study entry (Count of Participants) | ||||
| (0) Normal activity |
40
30.1%
|
22
32.8%
|
19
28.4%
|
81
30.3%
|
| (1) Restricted activity |
93
69.9%
|
45
67.2%
|
48
71.6%
|
186
69.7%
|
Outcome Measures
| Title | Objective Response Rate at 6 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab |
|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) |
| Measure Participants | 130 | 65 | 63 |
| Number (95% Confidence Interval) [% participants] |
7.7
5.8%
|
9.2
13.7%
|
1.6
2.4%
|
| Title | Objective Response Rate at 12 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab |
|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) |
| Measure Participants | 129 | 65 | 63 |
| Overall |
7.8
5.9%
|
9.2
13.7%
|
1.6
2.4%
|
| Current smoking/nicotine status - Total |
13.6
10.2%
|
14.3
21.3%
|
14.3
21.3%
|
| Current smoking/nicotine status - >10 pack years |
15.0
11.3%
|
14.3
21.3%
|
16.7
24.9%
|
| Current smoking/nicotine status - ≤10 pack years |
0
0%
|
0
0%
|
|
| Former smoking/nicotine status -Total |
6.8
5.1%
|
8.2
12.2%
|
0
0%
|
| Former smoking/nicotine status - >10 pack years |
5.2
3.9%
|
9.1
13.6%
|
0
0%
|
| Former smoking/nicotine status - ≤10 pack years |
10.0
7.5%
|
6.3
9.4%
|
0
0%
|
| Smoking/nicotine status - Never |
5.3
4%
|
11.1
16.6%
|
0
0%
|
| HPV status - Positive |
5.4
4.1%
|
16.7
24.9%
|
0
0%
|
| HPV status - Negative |
8.7
6.5%
|
6.4
9.6%
|
2.2
3.3%
|
| Title | Best Objective Response |
|---|---|
| Description | The best response a patient has had during their time in the study |
| Time Frame | After 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 129 | 65 | 63 | 257 |
| Response - Total |
7.8
5.9%
|
9.2
13.7%
|
1.6
2.4%
|
6.6
2.5%
|
| Response - Complete response (CR) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Response - Partial response (PR) |
7.8
5.9%
|
9.2
13.7%
|
1.6
2.4%
|
6.6
2.5%
|
| Non-response (NR) - Total |
92.2
69.3%
|
90.8
135.5%
|
98.4
146.9%
|
93.4
35%
|
| NR - Stable disease (SD) >=6 months (24 weeks) |
5.4
4.1%
|
6.2
9.3%
|
0
0%
|
4.3
1.6%
|
| NR - Unconfirmed complete or partial response (PR) |
1.6
1.2%
|
0
0%
|
0
0%
|
0.8
0.3%
|
| NR - Stable disease |
3.9
2.9%
|
6.2
9.3%
|
0
0%
|
3.5
1.3%
|
| NR - Progression |
64.3
48.3%
|
64.6
96.4%
|
69.8
104.2%
|
65.8
24.6%
|
| NR - Progression-RECIST 1.1 progression |
45.7
34.4%
|
46.2
69%
|
54.0
80.6%
|
47.9
17.9%
|
| NR - Progression-Death |
18.6
14%
|
18.5
27.6%
|
15.9
23.7%
|
17.9
6.7%
|
| NR - Not evaluable-Total |
22.5
16.9%
|
20.0
29.9%
|
28.6
42.7%
|
23.3
8.7%
|
| NR - Not evaluable-SD <6 months (24 weeks) |
20.2
15.2%
|
16.9
25.2%
|
19.0
28.4%
|
19.1
7.2%
|
| NR - Not evaluable-Incomplete post baseline tests |
2.3
1.7%
|
3.1
4.6%
|
9.5
14.2%
|
4.3
1.6%
|
| Title | Duration of Response - Participants Remaining in Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 10 | 6 | 1 | 17 |
| Percentage remaining in response-3 months |
90.0
67.7%
|
100
149.3%
|
100
149.3%
|
94.1
35.2%
|
| Percentage remaining in response-6 months |
70.0
52.6%
|
66.7
99.6%
|
100
149.3%
|
70.6
26.4%
|
| Percentage remaining in response-9 months |
58.3
43.8%
|
66.7
99.6%
|
NA
NaN
|
64.2
24%
|
| Percentage remaining in response-12 months |
46.7
35.1%
|
NA
NaN
|
NA
NaN
|
53.5
20%
|
| Percentage of ongoing response |
50.0
37.6%
|
66.7
99.6%
|
100
149.3%
|
58.8
22%
|
| Title | Time to Response |
|---|---|
| Description | Time to response in patients with objective response based on BICR assessments according to RECIST 1.1 |
| Time Frame | After 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 10 | 6 | 1 | 17 |
| Number of responders |
100
75.2%
|
100
149.3%
|
100
149.3%
|
100
37.5%
|
| Week 8, where response is first observed |
10.0
7.5%
|
0
0%
|
0
0%
|
5.9
2.2%
|
| Week 9, where response is first observed |
50.0
37.6%
|
16.7
24.9%
|
100
149.3%
|
41.2
15.4%
|
| Week 16, where response is first observed |
10.0
7.5%
|
16.7
24.9%
|
0
0%
|
11.8
4.4%
|
| Week 17, where response is first observed |
10.0
7.5%
|
16.7
24.9%
|
0
0%
|
11.8
4.4%
|
| Week 20, where response is first observed |
0
0%
|
16.7
24.9%
|
0
0%
|
5.9
2.2%
|
| Week 24, where response is first observed |
10.0
7.5%
|
16.7
24.9%
|
0
0%
|
11.8
4.4%
|
| Week 25, where response is first observed |
10.0
7.5%
|
16.7
24.9%
|
0
0%
|
11.8
4.4%
|
| Title | Time to Onset of Response From First Dose |
|---|---|
| Description | Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1 |
| Time Frame | After 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 10 | 6 | 1 | 17 |
| Median (Full Range) [Months] |
2.0
|
4.1
|
1.8
|
3.5
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 129 | 65 | 63 | 257 |
| METHOD 1: Disease control (DC) at 6 months |
13.2
9.9%
|
21.5
32.1%
|
1.6
2.4%
|
12.5
4.7%
|
| METHOD 1: No DC at 6 months |
86.8
65.3%
|
78.5
117.2%
|
98.4
146.9%
|
87.5
32.8%
|
| METHOD 1: No DC at 6 months-Not evaluable/missing |
20.2
15.2%
|
20.0
29.9%
|
22.2
33.1%
|
20.6
7.7%
|
| METHOD 2: DC at 6 months |
20.2
15.2%
|
26.2
39.1%
|
9.5
14.2%
|
19.1
7.2%
|
| METHOD 2: No DC at 6 months |
79.8
60%
|
73.8
110.1%
|
90.5
135.1%
|
80.9
30.3%
|
| METHOD 2: No DC at 6 months-Not evaluable/missing |
20.2
15.2%
|
20.0
29.9%
|
22.2
33.1%
|
20.6
7.7%
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 129 | 65 | 63 | 257 |
| DC at 12 months |
10.1
7.6%
|
12.3
18.4%
|
1.6
2.4%
|
8.6
3.2%
|
| No DC at 12 months |
89.9
67.6%
|
87.7
130.9%
|
98.4
146.9%
|
91.4
34.2%
|
| No DC at 12 months-Not evaluable/missing |
20.2
15.2%
|
20.0
29.9%
|
22.2
33.1%
|
20.6
7.7%
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set - all randomized patients |
| Arm/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 133 | 67 | 67 | 267 |
| Progression-Total |
82.0
61.7%
|
82.1
122.5%
|
88.1
131.5%
|
83.5
31.3%
|
| Total-RECIST 1.1 Progression |
57.9
43.5%
|
59.7
89.1%
|
67.2
100.3%
|
60.7
22.7%
|
| RECIST 1.1 progression-Target Lesions |
43.6
32.8%
|
43.3
64.6%
|
55.2
82.4%
|
46.4
17.4%
|
| RECIST 1.1 progression-Non-target lesions |
21.1
15.9%
|
26.9
40.1%
|
32.8
49%
|
25.5
9.6%
|
| RECIST 1.1 progression-New lesions |
26.3
19.8%
|
20.9
31.2%
|
26.9
40.1%
|
25.1
9.4%
|
| Progression-Death |
24.1
18.1%
|
22.4
33.4%
|
20.9
31.2%
|
22.8
8.5%
|
| No progression-Total |
18.0
13.5%
|
17.9
26.7%
|
11.9
17.8%
|
16.5
6.2%
|
| No progression-PD free and still being followed |
14.3
10.8%
|
13.4
20%
|
4.5
6.7%
|
11.6
4.3%
|
| No progression-Censored on Study Day 1 |
1.5
1.1%
|
0
0%
|
0
0%
|
0.7
0.3%
|
| No progression-Withdrawn consent |
0.8
0.6%
|
3.0
4.5%
|
1.5
2.2%
|
1.5
0.6%
|
| No progression- Censored death |
1.5
1.1%
|
1.5
2.2%
|
3.0
4.5%
|
1.9
0.7%
|
| No progression- Discontinued study |
0
0%
|
0
0%
|
3.0
4.5%
|
0.7
0.3%
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set - all randomized patients |
| Arm/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 133 | 67 | 67 | 267 |
| Progression-Total |
88.7
66.7%
|
83.6
124.8%
|
89.6
133.7%
|
87.6
32.8%
|
| Total-RECIST 1.1 Progression |
64.7
48.6%
|
59.7
89.1%
|
68.7
102.5%
|
64.4
24.1%
|
| RECIST 1.1 progression-Target Lesions |
50.4
37.9%
|
47.8
71.3%
|
56.7
84.6%
|
51.3
19.2%
|
| RECIST 1.1 progression-Non-target lesions |
23.3
17.5%
|
28.4
42.4%
|
32.8
49%
|
27.0
10.1%
|
| RECIST 1.1 progression-New lesions |
27.1
20.4%
|
23.9
35.7%
|
23.9
35.7%
|
25.5
9.6%
|
| Progression-Death |
24.1
18.1%
|
23.9
35.7%
|
20.9
31.2%
|
23.2
8.7%
|
| No progression-Total |
11.3
8.5%
|
16.4
24.5%
|
10.4
15.5%
|
12.4
4.6%
|
| No progression-PD free and still being followed |
6.8
5.1%
|
11.9
17.8%
|
3.0
4.5%
|
7.1
2.7%
|
| No progression-Censored death |
3.8
2.9%
|
0
0%
|
3.0
4.5%
|
2.6
1%
|
| No progression-Withdrawn consent |
0.8
0.6%
|
4.5
6.7%
|
1.5
2.2%
|
1.9
0.7%
|
| No progression-Discontinued study |
0
0%
|
0
0%
|
3.0
4.5%
|
0.7
0.3%
|
| Title | Overall Survival |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set - all randomized patients |
| Arm/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 133 | 67 | 67 | 267 |
| Death |
64.7
48.6%
|
65.7
98.1%
|
76.1
113.6%
|
67.8
25.4%
|
| Still in survival follow-up |
30.1
22.6%
|
28.4
42.4%
|
16.4
24.5%
|
26.2
9.8%
|
| Terminated prior to death |
5.3
4%
|
6.0
9%
|
7.5
11.2%
|
6.0
2.2%
|
| Terminated prior to death-Voluntary discon. |
5.3
4%
|
6.0
9%
|
4.5
6.7%
|
5.2
1.9%
|
| Terminated prior to death-Other |
0
0%
|
0
0%
|
3.0
4.5%
|
0.7
0.3%
|
| Title | Quality of Life |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set - all randomized patients |
| Arm/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab |
|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) |
| Measure Participants | 133 | 67 | 67 |
| EORTC QLQ-C30 Function-Physical |
12
|
13.6
|
5.1
|
| EORTC QLQ-C30 Function-Role |
16.3
|
16.7
|
11.8
|
| EORTC QLQ-C30 Function-Cognitive |
25
|
29.4
|
10.7
|
| EORTC QLQ-C30 Function-Emotional |
13.5
|
13.6
|
2.6
|
| EORTC QLQ-C30 Function-Social |
18.3
|
15.2
|
16.1
|
| EORTC QLQ-C30 Symptom-Fatigue |
16.8
|
17.3
|
7.5
|
| EORTC QLQ-C30 Symptom-Pain |
22.8
|
20.8
|
6.7
|
| EORTC QLQ-C30 Symptom-Nausea/vomiting |
22.2
|
16.7
|
17.6
|
| EORTC QLQ-C30 Global health status/QoL |
13.4
|
7.3
|
3.7
|
| EORTC QLQ-H&N35 Scale-Pain |
16.7
|
19.4
|
8.3
|
| EORTC QLQ-H&N35 Scale-Swallowing |
16.0
|
13.3
|
10.3
|
| EORTC QLQ-H&N35 Scale-Senses |
17.8
|
24.3
|
23.1
|
| EORTC QLQ-H&N35 Scale-Speech |
20.2
|
9.8
|
19.6
|
| EORTC QLQ-H&N35 Scale-Social eating |
21.3
|
20.0
|
15.0
|
| EORTC QLQ-H&N35 Scale-Social contact |
22.6
|
5.9
|
13.0
|
| EORTC QLQ-H&N35 Scale-Sexuality |
16.2
|
9.5
|
9.5
|
| Title | Duration of Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI4736 + Tremelimumab | MEDI4736 | Tremelimumab | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | Total across all treatment groups |
| Measure Participants | 10 | 6 | 1 | 17 |
| No. progressed or died within 12 months |
5
3.8%
|
2
3%
|
0
0%
|
7
2.6%
|
| No. progressed or died after 12 months |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | AEs and SAEs were collected from time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AEs were either spontaneously reported by the patient or reported in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated. AE and SAE data are reported using the Safety Analysis Set. | |||||
| Arm/Group Title | MEDI4736 AND TREMELIMUMAB COMBINATION | MEDI4736 | Tremelimumab | |||
| Arm/Group Description | 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 | MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses) | 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) | |||
All Cause Mortality |
||||||
| MEDI4736 AND TREMELIMUMAB COMBINATION | MEDI4736 | Tremelimumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 86/133 (64.7%) | 44/67 (65.7%) | 51/67 (76.1%) | |||
Serious Adverse Events |
||||||
| MEDI4736 AND TREMELIMUMAB COMBINATION | MEDI4736 | Tremelimumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 59/133 (44.4%) | 18/65 (27.7%) | 25/65 (38.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/133 (1.5%) | 3 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Cardiac disorders | ||||||
| Angina pectoris | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Atrial fibrillation | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Bradycardia | 1/133 (0.8%) | 2 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Cardiac arrest | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Cardiac failure | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Sinus tachycardia | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||
| Tracheo-oesophageal fistula | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Endocrine disorders | ||||||
| Hypothyroidism | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Lymphocytic hypophysitis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/133 (0.8%) | 1 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Autoimmune colitis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Colitis | 2/133 (1.5%) | 2 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Diarrhoea | 5/133 (3.8%) | 8 | 0/65 (0%) | 0 | 5/65 (7.7%) | 7 |
| Dysphagia | 1/133 (0.8%) | 1 | 1/65 (1.5%) | 1 | 2/65 (3.1%) | 3 |
| Impaired gastric emptying | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Intestinal obstruction | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Large intestine perforation | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Mouth haemorrhage | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Nausea | 3/133 (2.3%) | 4 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Oral cavity fistula | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Pneumatosis intestinalis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Rectal haemorrhage | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Small intestinal obstruction | 2/133 (1.5%) | 2 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Vomiting | 2/133 (1.5%) | 2 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| General disorders | ||||||
| Asthenia | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Death | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Face oedema | 1/133 (0.8%) | 1 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Fatigue | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| General physical health deterioration | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Pain | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Pyrexia | 3/133 (2.3%) | 3 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Hepatobiliary disorders | ||||||
| Hepatitis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 1/65 (1.5%) | 2 |
| Infections and infestations | ||||||
| Abdominal infection | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Abscess | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Bacteraemia | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Bronchitis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Cellulitis | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Clostridium difficile colitis | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Clostridium difficile infection | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 2 |
| Device related sepsis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Localised infection | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Lower respiratory tract infection | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Lung infection | 4/133 (3%) | 4 | 1/65 (1.5%) | 1 | 1/65 (1.5%) | 1 |
| Lymph gland infection | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Mastoiditis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Pneumonia | 9/133 (6.8%) | 10 | 1/65 (1.5%) | 1 | 1/65 (1.5%) | 2 |
| Pneumonia bacterial | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 2/65 (3.1%) | 2 |
| Pseudomonal sepsis | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Respiratory tract infection | 0/133 (0%) | 0 | 1/65 (1.5%) | 2 | 0/65 (0%) | 0 |
| Sepsis | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 1/65 (1.5%) | 1 |
| Septic rash | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Superinfection | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Upper respiratory tract infection | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Foreign body aspiration | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Gastrostomy tube site complication | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Hip fracture | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Humerus fracture | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Overdose | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Post procedural haemorrhage | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Tracheal obstruction | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Investigations | ||||||
| Platelet count decreased | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Weight decreased | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/133 (2.3%) | 3 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Dehydration | 4/133 (3%) | 5 | 1/65 (1.5%) | 1 | 1/65 (1.5%) | 1 |
| Failure to thrive | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Hypercalcaemia | 4/133 (3%) | 4 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Hypernatraemia | 2/133 (1.5%) | 2 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Hypokalaemia | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Malnutrition | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Back pain | 1/133 (0.8%) | 1 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Fistula | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Muscular weakness | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Pain in jaw | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Cancer pain | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Tumour pain | 2/133 (1.5%) | 2 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Nervous system disorders | ||||||
| Cerebrovascular accident | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Depressed level of consciousness | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Dizziness | 0/133 (0%) | 0 | 2/65 (3.1%) | 2 | 0/65 (0%) | 0 |
| Ischaemic stroke | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Neuropathy peripheral | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Presyncope | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Syncope | 1/133 (0.8%) | 2 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Transient ischaemic attack | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Product Issues | ||||||
| Device dislocation | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Psychiatric disorders | ||||||
| Agitation | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Confusional state | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Delirium | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Depression | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Renal and urinary disorders | ||||||
| Autoimmune nephritis | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Urinary retention | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Apnoea | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Bronchial obstruction | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Chronic obstructive pulmonary disease | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Dyspnoea | 4/133 (3%) | 4 | 1/65 (1.5%) | 1 | 2/65 (3.1%) | 2 |
| Emphysema | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Haemoptysis | 2/133 (1.5%) | 2 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Hypoxia | 1/133 (0.8%) | 1 | 1/65 (1.5%) | 1 | 1/65 (1.5%) | 1 |
| Increased bronchial secretion | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Pneumonia aspiration | 3/133 (2.3%) | 3 | 0/65 (0%) | 0 | 2/65 (3.1%) | 2 |
| Pneumonitis | 1/133 (0.8%) | 1 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Pulmonary embolism | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Respiratory failure | 2/133 (1.5%) | 2 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Tachypnoea | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Psoriasis | 0/133 (0%) | 0 | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 |
| Rash maculo-papular | 0/133 (0%) | 0 | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 |
| Vascular disorders | ||||||
| Exsanguination | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Hypotension | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
| Orthostatic hypotension | 1/133 (0.8%) | 1 | 0/65 (0%) | 0 | 0/65 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| MEDI4736 AND TREMELIMUMAB COMBINATION | MEDI4736 | Tremelimumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 110/133 (82.7%) | 52/65 (80%) | 59/65 (90.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 20/133 (15%) | 20 | 11/65 (16.9%) | 14 | 11/65 (16.9%) | 12 |
| Cardiac disorders | ||||||
| Tachycardia | 5/133 (3.8%) | 5 | 0/65 (0%) | 0 | 4/65 (6.2%) | 4 |
| Ear and labyrinth disorders | ||||||
| Ear pain | 3/133 (2.3%) | 3 | 2/65 (3.1%) | 2 | 4/65 (6.2%) | 4 |
| Endocrine disorders | ||||||
| Hypothyroidism | 15/133 (11.3%) | 15 | 9/65 (13.8%) | 9 | 6/65 (9.2%) | 6 |
| Gastrointestinal disorders | ||||||
| Constipation | 18/133 (13.5%) | 19 | 9/65 (13.8%) | 9 | 8/65 (12.3%) | 8 |
| Diarrhoea | 27/133 (20.3%) | 42 | 12/65 (18.5%) | 14 | 14/65 (21.5%) | 19 |
| Dysphagia | 14/133 (10.5%) | 15 | 8/65 (12.3%) | 9 | 6/65 (9.2%) | 7 |
| Nausea | 18/133 (13.5%) | 24 | 7/65 (10.8%) | 8 | 18/65 (27.7%) | 22 |
| Vomiting | 9/133 (6.8%) | 13 | 4/65 (6.2%) | 4 | 9/65 (13.8%) | 11 |
| General disorders | ||||||
| Asthenia | 21/133 (15.8%) | 24 | 10/65 (15.4%) | 12 | 8/65 (12.3%) | 11 |
| Fatigue | 25/133 (18.8%) | 29 | 19/65 (29.2%) | 23 | 12/65 (18.5%) | 12 |
| Mucosal inflammation | 1/133 (0.8%) | 1 | 4/65 (6.2%) | 4 | 1/65 (1.5%) | 2 |
| Oedema peripheral | 7/133 (5.3%) | 7 | 2/65 (3.1%) | 3 | 2/65 (3.1%) | 2 |
| Pain | 5/133 (3.8%) | 5 | 0/65 (0%) | 0 | 8/65 (12.3%) | 8 |
| Pyrexia | 16/133 (12%) | 19 | 5/65 (7.7%) | 5 | 12/65 (18.5%) | 16 |
| Investigations | ||||||
| Weight decreased | 18/133 (13.5%) | 18 | 5/65 (7.7%) | 5 | 8/65 (12.3%) | 9 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 25/133 (18.8%) | 27 | 10/65 (15.4%) | 11 | 10/65 (15.4%) | 11 |
| Dehydration | 6/133 (4.5%) | 10 | 0/65 (0%) | 0 | 6/65 (9.2%) | 6 |
| Hypercalcaemia | 7/133 (5.3%) | 8 | 6/65 (9.2%) | 7 | 3/65 (4.6%) | 3 |
| Hyperkalaemia | 2/133 (1.5%) | 2 | 4/65 (6.2%) | 4 | 2/65 (3.1%) | 2 |
| Hypoalbuminaemia | 2/133 (1.5%) | 3 | 1/65 (1.5%) | 1 | 4/65 (6.2%) | 4 |
| Hypokalaemia | 7/133 (5.3%) | 10 | 3/65 (4.6%) | 3 | 5/65 (7.7%) | 5 |
| Hypomagnesaemia | 5/133 (3.8%) | 6 | 5/65 (7.7%) | 5 | 5/65 (7.7%) | 5 |
| Hyponatraemia | 10/133 (7.5%) | 10 | 4/65 (6.2%) | 6 | 5/65 (7.7%) | 5 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 13/133 (9.8%) | 13 | 1/65 (1.5%) | 1 | 3/65 (4.6%) | 3 |
| Back pain | 9/133 (6.8%) | 10 | 5/65 (7.7%) | 5 | 1/65 (1.5%) | 1 |
| Musculoskeletal pain | 4/133 (3%) | 4 | 1/65 (1.5%) | 1 | 5/65 (7.7%) | 6 |
| Neck pain | 4/133 (3%) | 8 | 4/65 (6.2%) | 4 | 6/65 (9.2%) | 8 |
| Nervous system disorders | ||||||
| Dizziness | 4/133 (3%) | 5 | 3/65 (4.6%) | 3 | 5/65 (7.7%) | 6 |
| Headache | 6/133 (4.5%) | 7 | 6/65 (9.2%) | 7 | 7/65 (10.8%) | 7 |
| Paraesthesia | 3/133 (2.3%) | 3 | 5/65 (7.7%) | 5 | 1/65 (1.5%) | 1 |
| Psychiatric disorders | ||||||
| Anxiety | 1/133 (0.8%) | 1 | 3/65 (4.6%) | 3 | 4/65 (6.2%) | 4 |
| Insomnia | 9/133 (6.8%) | 9 | 3/65 (4.6%) | 3 | 2/65 (3.1%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 14/133 (10.5%) | 14 | 8/65 (12.3%) | 8 | 7/65 (10.8%) | 8 |
| Dyspnoea | 14/133 (10.5%) | 16 | 10/65 (15.4%) | 10 | 12/65 (18.5%) | 12 |
| Productive cough | 4/133 (3%) | 5 | 6/65 (9.2%) | 6 | 5/65 (7.7%) | 6 |
| Skin and subcutaneous tissue disorders | ||||||
| Dry skin | 5/133 (3.8%) | 6 | 5/65 (7.7%) | 5 | 1/65 (1.5%) | 1 |
| Pruritus | 14/133 (10.5%) | 15 | 6/65 (9.2%) | 6 | 4/65 (6.2%) | 4 |
| Rash | 10/133 (7.5%) | 11 | 3/65 (4.6%) | 3 | 5/65 (7.7%) | 6 |
| Vascular disorders | ||||||
| Hypertension | 8/133 (6%) | 11 | 6/65 (9.2%) | 7 | 1/65 (1.5%) | 1 |
| Hypotension | 7/133 (5.3%) | 7 | 0/65 (0%) | 0 | 5/65 (7.7%) | 5 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review publications prior to public release for a period up to 120 days to confirm accuracy, prevent disclosure of confidential information, and ensure that information is handled appropriately.
Results Point of Contact
| Name/Title | Jean Fan, MD, Global Clinical Lead |
|---|---|
| Organization | AstraZeneca LP |
| Phone | 1-301-398-5080 |
| jean.fan@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02319044
Other Study ID Numbers:
- D4193C00003
First Posted:
Dec 18, 2014
Last Update Posted:
Sep 29, 2020
Last Verified:
Sep 1, 2020