KESTREL: Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02551159
Collaborator
(none)
823
197
3
67.2
4.2
0.1
Study Details
Study Description
Brief Summary
This is a randomized, open-label, multi-center, 3-arm, global Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination or MEDI4736 monotherapy versus SoC (EXTREME regimen) in the treatment of patients with SCCHN who have not received prior systemic chemotherapy for recurrent or metastatic disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Patients will be randomized in a 2:1:1 ratio to MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or SoC. Patients in all arms will continue therapy until progression. Tumor assessments will be performed on computed tomography scans or magnetic resonance imaging scans, preferably with intravenous (IV) contrast. Efficacy for all patients will be assessed by objective tumor assessments every 6 weeks for the first 24 weeks, then every 8 weeks thereafter until treatment discontinuation due to progression or toxicity. All patients will be followed every 3 months for survival after progression is confirmed.
Study Design
Study Type:
Interventional
Actual Enrollment
:
823 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized, Open-label, Multi-center, Global Study of MEDI4736 Alone or in Combination With Tremelimumab Versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients
Actual Study Start Date
:
Oct 15, 2015
Actual Primary Completion Date
:
Jul 6, 2020
Actual Study Completion Date
:
May 21, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Monotherapy MEDI4736 monotherapy. |
Biological: MEDI4736
Anti-PD-L1 antibody
|
| Experimental: Combination Therapy MEDI4736+Tremelimumab combination therapy |
Biological: Tremelimumab
Anti-CTLA-4 Antibody
Biological: MEDI4736+Tremelimumab
|
| Active Comparator: Standard of Care Standard of Care treatment |
Biological: Cetuximab
Monoclonal Antibody
Drug: 5-fluorouracil (5FU)
Chemotherapy Agent
Drug: Cisplatin
Chemotherapy agent
Drug: Carboplatin
Chemotherapy Agent
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) [From date of randomization until time of final analysis, an average of approximately 4 years]
Number of participants with Overall Survival (OS)
- Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup [From date of randomization until time of final analysis, an average of approximately 4 years]
Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
Secondary Outcome Measures
- Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC) [From date of randomization until time of final analysis, an average of approximately 4 years]
Number of participants with Overall Survival (OS)
- Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup [12, 18 and 24 months after randomization]
Percentage of patients alive
- Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup [Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years]
Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup [Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years]
Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: >= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR)
- Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup [Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years]
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
- Overall Survival (OS) Status in the All-comers (Full Analysis Set) [From date of randomization until time of final analysis, an average of approximately 4 years]
Number of participants with Overall Survival (OS)
- Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set) [From date of randomization until time of final analysis, an average of approximately 4 years]
Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
- Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) [12, 18 and 24 months after randomization]
Percentage of patients alive
- Progression Free Survival (PFS) in the All-comers (Full Analysis Set) [Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years]
Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Objective Response Rate (ORR) in the All-comers (Full Analysis Set) [Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years]
Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: >= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR)
- Duration of Response (DoR) in the All-comers (Full Analysis Set) [Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years]
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age ≥18 years at the time of screening
-
Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx).
-
A fresh tumor biopsy for the purpose of screening or an available archival tumor sample. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy.
-
No prior systemic chemotherapy for recurrent or metastatic disease
-
World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
-
No prior exposure to immune-mediated therapy,
Exclusion Criteria:
-
Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland)
-
Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting
-
Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment
-
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Aurora | Colorado | United States | 80045 |
| 2 | Research Site | Washington | District of Columbia | United States | 20007 |
| 3 | Research Site | Fort Myers | Florida | United States | 33916 |
| 4 | Research Site | Saint Petersburg | Florida | United States | 33705 |
| 5 | Research Site | Tampa | Florida | United States | 33612 |
| 6 | Research Site | Atlanta | Georgia | United States | 30322 |
| 7 | Research Site | Chicago | Illinois | United States | 60637 |
| 8 | Research Site | Baltimore | Maryland | United States | 21201 |
| 9 | Research Site | Baltimore | Maryland | United States | 21231 |
| 10 | Research Site | Boston | Massachusetts | United States | 02215 |
| 11 | Research Site | Morristown | New Jersey | United States | 07960 |
| 12 | Research Site | New York | New York | United States | 10029 |
| 13 | Research Site | New York | New York | United States | 10065 |
| 14 | Research Site | Chapel Hill | North Carolina | United States | 27599 |
| 15 | Research Site | Charlotte | North Carolina | United States | 28204 |
| 16 | Research Site | Winston-Salem | North Carolina | United States | 27157 |
| 17 | Research Site | Cleveland | Ohio | United States | 44115 |
| 18 | Research Site | Columbus | Ohio | United States | 43210 |
| 19 | Research Site | Nashville | Tennessee | United States | 37203 |
| 20 | Research Site | Graz | Austria | 8036 | |
| 21 | Research Site | Innsbruck | Austria | 6020 | |
| 22 | Research Site | Linz | Austria | 4010 | |
| 23 | Research Site | Wien | Austria | 1140 | |
| 24 | Research Site | Brussels | Belgium | 1000 | |
| 25 | Research Site | Brussels | Belgium | 1090 | |
| 26 | Research Site | Bruxelles | Belgium | 1200 | |
| 27 | Research Site | Leuven | Belgium | 3000 | |
| 28 | Research Site | Namur | Belgium | 5000 | |
| 29 | Research Site | Barretos | Brazil | 14784-400 | |
| 30 | Research Site | Curitiba | Brazil | 81520-060 | |
| 31 | Research Site | Florianópolis | Brazil | 88034-000 | |
| 32 | Research Site | Ijui | Brazil | 98700-000 | |
| 33 | Research Site | Porto Alegre | Brazil | 90035-003 | |
| 34 | Research Site | Porto Alegre | Brazil | 90619-900 | |
| 35 | Research Site | Porto Alegre | Brazil | 91350-200 | |
| 36 | Research Site | Recife | Brazil | 50040-000 | |
| 37 | Research Site | Rio de Janeiro | Brazil | 22793-080 | |
| 38 | Research Site | Santo Andre | Brazil | 09080-110 | |
| 39 | Research Site | Santo André | Brazil | 09060-650 | |
| 40 | Research Site | São José do Rio Preto | Brazil | 15090-000 | |
| 41 | Research Site | São Paulo | Brazil | 03102-002 | |
| 42 | Research Site | Calgary | Alberta | Canada | T2N 4N2 |
| 43 | Research Site | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 44 | Research Site | Moncton | New Brunswick | Canada | E1C 8X3 |
| 45 | Research Site | Halifax | Nova Scotia | Canada | B3H 1V7 |
| 46 | Research Site | Hamilton | Ontario | Canada | L8V 5C2 |
| 47 | Research Site | London | Ontario | Canada | N6A 4L6 |
| 48 | Research Site | Ottawa | Ontario | Canada | K1H 8L6 |
| 49 | Research Site | Toronto | Ontario | Canada | M5G 2M9 |
| 50 | Research Site | Montreal | Quebec | Canada | H4A 3J1 |
| 51 | Research Site | Bordeaux | France | 33000 | |
| 52 | Research Site | Brest | France | 29200 | |
| 53 | Research Site | Dijon | France | 21079 | |
| 54 | Research Site | Lyon Cedex 08 | France | 69373 | |
| 55 | Research Site | Nice | France | 06100 | |
| 56 | Research Site | Paris | France | 75015 | |
| 57 | Research Site | Poitiers Cedex | France | 86021 | |
| 58 | Research Site | Toulouse Cedex | France | 31059 | |
| 59 | Research Site | Vandoeuvre les Nancy | France | 54519 | |
| 60 | Research Site | Villejuif | France | 94800 | |
| 61 | Research Site | Berlin | Germany | 12203 | |
| 62 | Research Site | Erlangen | Germany | 91054 | |
| 63 | Research Site | Essen | Germany | 45147 | |
| 64 | Research Site | Frankfurt am Main | Germany | 60590 | |
| 65 | Research Site | Freiburg | Germany | 79106 | |
| 66 | Research Site | Hamburg | Germany | 20246 | |
| 67 | Research Site | Heidelberg | Germany | 69120 | |
| 68 | Research Site | Mainz | Germany | 55131 | |
| 69 | Research Site | Tübingen | Germany | 72076 | |
| 70 | Research Site | Würzburg | Germany | 97070 | |
| 71 | Research Site | Athens | Greece | 115 22 | |
| 72 | Research Site | Athens | Greece | 11527 | |
| 73 | Research Site | Athens | Greece | 124 61 | |
| 74 | Research Site | Athens | Greece | 18547 | |
| 75 | Research Site | Heraklion | Greece | 711 11 | |
| 76 | Research Site | Thessaloniki | Greece | 54645 | |
| 77 | Research Site | Bangalore | India | 560027 | |
| 78 | Research Site | Bangalore | India | 560076 | |
| 79 | Research Site | Bengaluru | India | 560076 | |
| 80 | Research Site | Gurgaon | India | 122001 | |
| 81 | Research Site | Karamsad | India | 388325 | |
| 82 | Research Site | Madurai | India | 625107 | |
| 83 | Research Site | Pune | India | 411001 | |
| 84 | Research Site | Cona | Italy | 44124 | |
| 85 | Research Site | Firenze | Italy | 50134 | |
| 86 | Research Site | Messina | Italy | 98158 | |
| 87 | Research Site | Milano | Italy | 20133 | |
| 88 | Research Site | Padova | Italy | 35128 | |
| 89 | Research Site | Palermo | Italy | 90127 | |
| 90 | Research Site | Salerno | Italy | 84131 | |
| 91 | Research Site | Siena | Italy | 53100 | |
| 92 | Research Site | Torino | Italy | 10126 | |
| 93 | Research Site | Akashi-shi | Japan | 673-8558 | |
| 94 | Research Site | Chiba-shi | Japan | 260-8717 | |
| 95 | Research Site | Fukuoka-shi | Japan | 811-1347 | |
| 96 | Research Site | Hirakata-shi | Japan | 573-1191 | |
| 97 | Research Site | Isehara-shi | Japan | 259-1193 | |
| 98 | Research Site | Kagoshima-shi | Japan | 890-8520 | |
| 99 | Research Site | Kanazawa-shi | Japan | 920-8650 | |
| 100 | Research Site | Kitaadachi-gun | Japan | 362-0806 | |
| 101 | Research Site | Kobe-shi | Japan | 650-0017 | |
| 102 | Research Site | Koto-ku | Japan | 135-8550 | |
| 103 | Research Site | Natori-shi | Japan | 981-1293 | |
| 104 | Research Site | Okayama-shi | Japan | 700-8558 | |
| 105 | Research Site | Osaka-shi | Japan | 541-8567 | |
| 106 | Research Site | Osakasayama | Japan | 589-8511 | |
| 107 | Research Site | Sapporo-shi | Japan | 003-0804 | |
| 108 | Research Site | Sapporo | Japan | 060-8648 | |
| 109 | Research Site | Sunto-gun | Japan | 411-8777 | |
| 110 | Research Site | Takatsuki-shi | Japan | 569-8686 | |
| 111 | Research Site | Toyoake-shi | Japan | 470-1192 | |
| 112 | Research Site | Yokohama-shi | Japan | 241-8515 | |
| 113 | Research Site | Cheongju-si | Korea, Republic of | 28644 | |
| 114 | Research Site | Hwasun-gun | Korea, Republic of | 58128 | |
| 115 | Research Site | Incheon | Korea, Republic of | 21565 | |
| 116 | Research Site | Seo-Gu | Korea, Republic of | 49241 | |
| 117 | Research Site | Seongnam-si | Korea, Republic of | 13620 | |
| 118 | Research Site | Seoul | Korea, Republic of | 03080 | |
| 119 | Research Site | Seoul | Korea, Republic of | 03722 | |
| 120 | Research Site | Seoul | Korea, Republic of | 05505 | |
| 121 | Research Site | Seoul | Korea, Republic of | 135-710 | |
| 122 | Research Site | Suwon-si | Korea, Republic of | 16499 | |
| 123 | Research Site | Cebu City | Philippines | 6000 | |
| 124 | Research Site | Las Pinas | Philippines | 1740 | |
| 125 | Research Site | Quezon City | Philippines | 1112 | |
| 126 | Research Site | Białystok | Poland | 15-027 | |
| 127 | Research Site | Bielsko-Biała | Poland | 43-300 | |
| 128 | Research Site | Gdańsk | Poland | 80-214 | |
| 129 | Research Site | Gdynia | Poland | 81-519 | |
| 130 | Research Site | Lublin | Poland | 20-090 | |
| 131 | Research Site | Poznan | Poland | 60-780 | |
| 132 | Research Site | Poznan | Poland | 61-866 | |
| 133 | Research Site | Szczecin | Poland | 71-730 | |
| 134 | Research Site | Warszawa | Poland | 02-781 | |
| 135 | Research Site | Łódź | Poland | 93-513 | |
| 136 | Research Site | Suceava | Romania | 720237 | |
| 137 | Research Site | Arkhangelsk | Russian Federation | 163045 | |
| 138 | Research Site | Ekaterinburg | Russian Federation | 620905 | |
| 139 | Research Site | Krasnodar | Russian Federation | 350040 | |
| 140 | Research Site | Moscow | Russian Federation | 125367 | |
| 141 | Research Site | Obninsk | Russian Federation | 249036 | |
| 142 | Research Site | Omsk | Russian Federation | 644013 | |
| 143 | Research Site | Saint Petersburg | Russian Federation | 195271 | |
| 144 | Research Site | Saint Petersburg | Russian Federation | 198255 | |
| 145 | Research Site | Saint-Petersburg | Russian Federation | 197758 | |
| 146 | Research Site | Sochi | Russian Federation | 354057 | |
| 147 | Research Site | St.Petersburg | Russian Federation | 191014 | |
| 148 | Research Site | Ufa | Russian Federation | 450054 | |
| 149 | Research Site | Bratislava | Slovakia | 833 01 | |
| 150 | Research Site | Kosice | Slovakia | 041 91 | |
| 151 | Research Site | Badajoz | Spain | 06008 | |
| 152 | Research Site | Barcelona | Spain | 08035 | |
| 153 | Research Site | Barcelona | Spain | 08036 | |
| 154 | Research Site | Jaén | Spain | 23007 | |
| 155 | Research Site | L'Hospitalet de Llobregat | Spain | 08907 | |
| 156 | Research Site | Madrid | Spain | 28007 | |
| 157 | Research Site | Madrid | Spain | 28034 | |
| 158 | Research Site | Madrid | Spain | 28040 | |
| 159 | Research Site | Madrid | Spain | 28050 | |
| 160 | Research Site | Marbella | Spain | 29600 | |
| 161 | Research Site | Málaga | Spain | 29010 | |
| 162 | Research Site | Valencia | Spain | 46026 | |
| 163 | Research Site | Zaragoza | Spain | 50009 | |
| 164 | Research Site | Kaohsiung | Taiwan | ||
| 165 | Research Site | Taichung | Taiwan | 40447 | |
| 166 | Research Site | Taichung | Taiwan | 40705 | |
| 167 | Research Site | Tainan | Taiwan | 704 | |
| 168 | Research Site | Taipei | Taiwan | 100 | |
| 169 | Research Site | Taipei | Taiwan | 10449 | |
| 170 | Research Site | Taipei | Taiwan | 11217 | |
| 171 | Research Site | Bangkok | Thailand | 10330 | |
| 172 | Research Site | Bangkok | Thailand | 10700 | |
| 173 | Research Site | Chiang Mai | Thailand | 50200 | |
| 174 | Research Site | Hat Yai | Thailand | 90110 | |
| 175 | Research Site | Pathumthani | Thailand | 12120 | |
| 176 | Research Site | Dnipro | Ukraine | 49102 | |
| 177 | Research Site | Ivano-Frankivsk | Ukraine | 76018 | |
| 178 | Research Site | Kapitanivka Village | Ukraine | 08111 | |
| 179 | Research Site | Kharkiv Region | Ukraine | 61070 | |
| 180 | Research Site | Kirovohrad | Ukraine | 25006 | |
| 181 | Research Site | Kryvyi Rih | Ukraine | 50048 | |
| 182 | Research Site | Kyiv | Ukraine | 03022 | |
| 183 | Research Site | Kyiv | Ukraine | 03115 | |
| 184 | Research Site | Odesa | Ukraine | 65055 | |
| 185 | Research Site | Sumy | Ukraine | 40022 | |
| 186 | Research Site | Vinnytsia | Ukraine | 21029 | |
| 187 | Research Site | Bebington | United Kingdom | CH63 4JY | |
| 188 | Research Site | Birmingham | United Kingdom | B15 2TT | |
| 189 | Research Site | London | United Kingdom | EC1A 7BE | |
| 190 | Research Site | London | United Kingdom | SW3 6JJ | |
| 191 | Research Site | Manchester | United Kingdom | M20 4BX | |
| 192 | Research Site | Sutton | United Kingdom | SM2 5PT | |
| 193 | Research Site | Taunton | United Kingdom | TA1 5DA | |
| 194 | Research Site | Ha Noi | Vietnam | 100000 | |
| 195 | Research Site | Hanoi | Vietnam | 100000 | |
| 196 | Research Site | Hanoi | Vietnam | ||
| 197 | Research Site | Ho Chi Minh city | Vietnam | 700000 |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Richard Olsson,
- Principal Investigator: Tanguy Seiwert, The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02551159
Other Study ID Numbers:
- D419LC00001
First Posted:
Sep 16, 2015
Last Update Posted:
Oct 13, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Patients meeting all the eligibility criteria were randomized 2:1:1 to durvalumab plus tremelimumab combination therapy, durvalumab monotherapy or standard of care. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Period Title: Overall Study | |||
| STARTED | 413 | 204 | 206 |
| Full Analysis Set | 413 | 204 | 206 |
| Safety Analysis Set | 408 | 202 | 196 |
| PD-L1 TC/IC High Subgroup Analysis Set | 190 | 99 | 94 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 413 | 204 | 206 |
Baseline Characteristics
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) | Total |
|---|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent | Total of all reporting groups |
| Overall Participants | 413 | 204 | 206 | 823 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
60.5
(9.56)
|
60.2
(10.41)
|
60.9
(9.45)
|
60.5
(9.74)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
73
17.7%
|
29
14.2%
|
32
15.5%
|
134
16.3%
|
| Male |
340
82.3%
|
175
85.8%
|
174
84.5%
|
689
83.7%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||
| White |
298
72.2%
|
145
71.1%
|
160
77.7%
|
603
73.3%
|
| Black or African American |
5
1.2%
|
3
1.5%
|
2
1%
|
10
1.2%
|
| Asian |
109
26.4%
|
54
26.5%
|
42
20.4%
|
205
24.9%
|
| Other |
0
0%
|
2
1%
|
2
1%
|
4
0.5%
|
| Missing |
1
0.2%
|
0
0%
|
0
0%
|
1
0.1%
|
Outcome Measures
| Title | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) |
|---|---|
| Description | Number of participants with Overall Survival (OS) |
| Time Frame | From date of randomization until time of final analysis, an average of approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD-L1 TC/IC subgroup |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 190 | 99 | 94 |
| Death |
162
39.2%
|
84
41.2%
|
77
37.4%
|
| Voluntary Discontinuation by subject |
1
0.2%
|
1
0.5%
|
3
1.5%
|
| Alive or lost to follow up |
27
6.5%
|
14
6.9%
|
14
6.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab, Standard of Care (SOC) |
|---|---|---|
| Comments | Statistical analysis of number of deaths | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.787 |
| Comments | 2 sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.96 | |
| Confidence Interval |
(2-Sided) 95% 0.69 to 1.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup |
|---|---|
| Description | Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1) |
| Time Frame | From date of randomization until time of final analysis, an average of approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD-L1 TC/IC subgroup |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 190 | 99 | 94 |
| Median (95% Confidence Interval) [Months] |
11.2
|
10.9
|
10.9
|
| Title | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC) |
|---|---|
| Description | Number of participants with Overall Survival (OS) |
| Time Frame | From date of randomization until time of final analysis, an average of approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD-L1 TC/IC subgroup |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 190 | 99 | 94 |
| Count of Participants [Participants] |
162
39.2%
|
84
41.2%
|
77
37.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab + Tremelimumab, Standard of Care (SOC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.634 |
| Comments | 2 sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.05 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 1.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup |
|---|---|
| Description | Percentage of patients alive |
| Time Frame | 12, 18 and 24 months after randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD-L1 TC/IC subgroup |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 190 | 99 | 94 |
| at 12 months |
49.3
11.9%
|
48.0
23.5%
|
44.0
21.4%
|
| at 18 months |
31.8
7.7%
|
34.7
17%
|
30.8
15%
|
| at 24 months |
23.9
5.8%
|
27.6
13.5%
|
26.4
12.8%
|
| Title | Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup |
|---|---|
| Description | Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Time Frame | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD-L1 TC/IC subgroup |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 190 | 99 | 94 |
| Median (95% Confidence Interval) [Months] |
2.8
|
2.8
|
5.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab, Standard of Care (SOC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.287 |
| Comments | 2 sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.30 | |
| Confidence Interval |
(2-Sided) 95% 0.94 to 1.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab + Tremelimumab, Standard of Care (SOC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.028 |
| Comments | 2 sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.32 | |
| Confidence Interval |
(2-Sided) 95% 0.99 to 1.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup |
|---|---|
| Description | Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: >= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR) |
| Time Frame | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD-L1 TC/IC subgroup |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 190 | 99 | 94 |
| Response |
48
11.6%
|
16
7.8%
|
47
22.8%
|
| No response |
142
34.4%
|
83
40.7%
|
47
22.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab, Standard of Care (SOC) |
|---|---|---|
| Comments | Statistical analysis of number with a response | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2 sided | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.19 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 0.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab + Tremelimumab, Standard of Care (SOC) |
|---|---|---|
| Comments | Statistical analysis of number with a response | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2 sided | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.34 | |
| Confidence Interval |
(2-Sided) 95% 0.20 to 0.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup |
|---|---|
| Description | Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression |
| Time Frame | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD-L1 TC/IC subgroup |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 48 | 16 | 47 |
| Median (95% Confidence Interval) [Months] |
6.5
|
12.3
|
4.2
|
| Title | Overall Survival (OS) Status in the All-comers (Full Analysis Set) |
|---|---|
| Description | Number of participants with Overall Survival (OS) |
| Time Frame | From date of randomization until time of final analysis, an average of approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-comers (Full analysis set) |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 413 | 204 | 206 |
| Death |
356
86.2%
|
176
86.3%
|
171
83%
|
| Voluntary Discontinuation by subject |
4
1%
|
3
1.5%
|
6
2.9%
|
| Alive or lost to follow up |
53
12.8%
|
25
12.3%
|
29
14.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab, Standard of Care (SOC) |
|---|---|---|
| Comments | Statistical analysis of number of deaths | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.811 |
| Comments | 2 sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.83 to 1.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab + Tremelimumab, Standard of Care (SOC) |
|---|---|---|
| Comments | Statistical analysis of number of deaths | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.624 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.04 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set) |
|---|---|
| Description | Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1) |
| Time Frame | From date of randomization until time of final analysis, an average of approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-comers (Full analysis set) |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 413 | 204 | 206 |
| Median (95% Confidence Interval) [Months] |
10.7
|
9.9
|
10.3
|
| Title | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) |
|---|---|
| Description | Percentage of patients alive |
| Time Frame | 12, 18 and 24 months after randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-comers (Full analysis set) |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 413 | 204 | 206 |
| at 12 months |
46.5
11.3%
|
42.8
21%
|
43.8
21.3%
|
| at 18 months |
30.7
7.4%
|
31.2
15.3%
|
29.7
14.4%
|
| at 24 months |
22.9
5.5%
|
24.7
12.1%
|
23.2
11.3%
|
| Title | Progression Free Survival (PFS) in the All-comers (Full Analysis Set) |
|---|---|
| Description | Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Time Frame | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-comers (Full analysis set) |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 413 | 204 | 206 |
| Median (95% Confidence Interval) [Months] |
2.8
|
2.8
|
5.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab, Standard of Care (SOC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | 2 sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.36 | |
| Confidence Interval |
(2-Sided) 95% 1.10 to 1.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab + Tremelimumab, Standard of Care (SOC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | 2 sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 1.06 to 1.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Response Rate (ORR) in the All-comers (Full Analysis Set) |
|---|---|
| Description | Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: >= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR) |
| Time Frame | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-comers (Full analysis set) |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 413 | 204 | 206 |
| Response |
90
21.8%
|
35
17.2%
|
101
49%
|
| No response |
323
78.2%
|
169
82.8%
|
105
51%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab, Standard of Care (SOC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2 sided | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.21 | |
| Confidence Interval |
(2-Sided) 95% 0.13 to 0.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Durvalumab + Tremelimumab, Standard of Care (SOC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2 sided | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.29 | |
| Confidence Interval |
(2-Sided) 95% 0.20 to 0.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Response (DoR) in the All-comers (Full Analysis Set) |
|---|---|
| Description | Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression |
| Time Frame | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-comers (Full analysis set) |
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) |
|---|---|---|---|
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent |
| Measure Participants | 90 | 35 | 101 |
| Median (95% Confidence Interval) [Months] |
9.2
|
11.9
|
4.2
|
Adverse Events
| Time Frame | Adverse events and serious adverse events will be collected from the time of signature of informed consent throughout the treatment period and including the follow-up period (up to 90 days after the last dose of investigational product or until initiation of another therapy) for an average of approximately 4 years. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) | |||
| Arm/Group Description | tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent | |||
All Cause Mortality |
||||||
| Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 356/413 (86.2%) | 176/204 (86.3%) | 171/206 (83%) | |||
Serious Adverse Events |
||||||
| Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 168/408 (41.2%) | 78/202 (38.6%) | 94/196 (48%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 3/196 (1.5%) | 3 |
| Blood loss anaemia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Pancytopenia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Thrombocytopenia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 5/196 (2.6%) | 5 |
| Febrile bone marrow aplasia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 2/196 (1%) | 2 |
| Febrile neutropenia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 8/196 (4.1%) | 9 |
| Leukopenia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 4/196 (2%) | 6 |
| Lymph node haemorrhage | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Neutropenia | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 5/196 (2.6%) | 5 |
| Cardiac disorders | ||||||
| Cardiac arrest | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 2/196 (1%) | 2 |
| Cardiac failure | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Supraventricular tachycardia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Acute coronary syndrome | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Acute myocardial infarction | 0/408 (0%) | 0 | 2/202 (1%) | 2 | 0/196 (0%) | 0 |
| Atrial fibrillation | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Atrial flutter | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Cardio-respiratory arrest | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Cardiomyopathy | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Cardiopulmonary failure | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Myocardial infarction | 1/408 (0.2%) | 1 | 2/202 (1%) | 2 | 0/196 (0%) | 0 |
| Tachycardia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Endocrine disorders | ||||||
| Adrenal insufficiency | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Hypopituitarism | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Hypothyroidism | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Colitis | 4/408 (1%) | 4 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Diarrhoea | 9/408 (2.2%) | 14 | 2/202 (1%) | 2 | 4/196 (2%) | 4 |
| Duodenal ulcer haemorrhage | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Enteritis | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Enterocolitis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Gastric haemorrhage | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Gastric perforation | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Gastric ulcer perforation | 0/408 (0%) | 0 | 2/202 (1%) | 2 | 0/196 (0%) | 0 |
| Inguinal hernia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Obstructive pancreatitis | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Oesophagitis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Constipation | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Duodenal ulcer perforation | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Dysphagia | 6/408 (1.5%) | 6 | 1/202 (0.5%) | 1 | 5/196 (2.6%) | 5 |
| Gastritis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 2/196 (1%) | 2 |
| Haematemesis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Ileus paralytic | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Intestinal haemorrhage | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Intestinal ischaemia | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Large intestine perforation | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Mouth haemorrhage | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Nausea | 5/408 (1.2%) | 5 | 0/202 (0%) | 0 | 2/196 (1%) | 2 |
| Oral pain | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Pneumatosis intestinalis | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Pneumoperitoneum | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Proctitis | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Rectal haemorrhage | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Small intestinal obstruction | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Tongue oedema | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Vomiting | 8/408 (2%) | 12 | 1/202 (0.5%) | 2 | 2/196 (1%) | 2 |
| General disorders | ||||||
| Death | 2/408 (0.5%) | 2 | 4/202 (2%) | 4 | 2/196 (1%) | 2 |
| Malaise | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Mucosal inflammation | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 4/196 (2%) | 5 |
| Asthenia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Complication associated with device | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Face oedema | 1/408 (0.2%) | 1 | 3/202 (1.5%) | 3 | 0/196 (0%) | 0 |
| Fatigue | 3/408 (0.7%) | 3 | 2/202 (1%) | 3 | 2/196 (1%) | 2 |
| General physical health deterioration | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Hyperthermia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Multiple organ dysfunction syndrome | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Oedema | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Oedema peripheral | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Pyrexia | 6/408 (1.5%) | 7 | 3/202 (1.5%) | 3 | 2/196 (1%) | 2 |
| Soft tissue inflammation | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Sudden death | 3/408 (0.7%) | 3 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Autoimmune hepatitis | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Hepatic function abnormal | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Hepatitis | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Hepatocellular injury | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Hepatorenal failure | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Immune-mediated hepatitis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Immune system disorders | ||||||
| Anaphylactic reaction | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 3/196 (1.5%) | 3 |
| Drug hypersensitivity | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Infections and infestations | ||||||
| Oral infection | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Superinfection | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Tracheitis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Upper respiratory tract infection | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Abdominal infection | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Abscess neck | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Acute sinusitis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Bacterial infection | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Bacterial sepsis | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Bronchitis | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Cellulitis | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Clostridium difficile infection | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Device related infection | 2/408 (0.5%) | 2 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Ear infection | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Escherichia urinary tract infection | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Fungal infection | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Gangrene | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Gastroenteritis | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Herpes zoster | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Infection | 5/408 (1.2%) | 5 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Lower respiratory tract infection | 4/408 (1%) | 4 | 1/202 (0.5%) | 1 | 2/196 (1%) | 2 |
| Lung abscess | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Mucosal infection | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Oesophageal candidiasis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Oral candidiasis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Parotitis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Pneumocystis jirovecii pneumonia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Pneumonia | 32/408 (7.8%) | 33 | 14/202 (6.9%) | 14 | 13/196 (6.6%) | 13 |
| Pneumonia staphylococcal | 2/408 (0.5%) | 2 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Pyelonephritis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Rash pustular | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Respiratory tract infection | 5/408 (1.2%) | 5 | 2/202 (1%) | 2 | 2/196 (1%) | 3 |
| Respiratory tract infection bacterial | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Sepsis | 5/408 (1.2%) | 5 | 1/202 (0.5%) | 1 | 4/196 (2%) | 4 |
| Septic shock | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 2/196 (1%) | 2 |
| Skin infection | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Soft tissue infection | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Staphylococcal infection | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Tracheobronchitis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Viral infection | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Wound infection | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Carbon monoxide poisoning | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Fall | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Gastrostomy failure | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Hip fracture | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Infusion related reaction | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 2/196 (1%) | 2 |
| Rib fracture | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Road traffic accident | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Femoral neck fracture | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Overdose | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Post procedural fistula | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Post procedural haemorrhage | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Tracheal obstruction | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Amylase increased | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Troponin t increased | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Aspartate aminotransferase increased | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Blood glucose increased | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Lipase increased | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Neutrophil count decreased | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 2 |
| Weight decreased | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| White blood cell count decreased | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 3/196 (1.5%) | 3 |
| Hypercalcaemia | 1/408 (0.2%) | 3 | 1/202 (0.5%) | 2 | 2/196 (1%) | 2 |
| Hyperglycaemia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Hyperkalaemia | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Hypokalaemia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Cachexia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Decreased appetite | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Diabetic ketoacidosis | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Hypocalcaemia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Hypoglycaemia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Hypomagnesaemia | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 2/196 (1%) | 2 |
| Hyponatraemia | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Hypophagia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Malnutrition | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Type 2 diabetes mellitus | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Autoimmune myositis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Musculoskeletal chest pain | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Osteonecrosis of jaw | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Arthralgia | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Back pain | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Osteolysis | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Rhabdomyolysis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Trismus | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Infected neoplasm | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Renal cancer | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Basal cell carcinoma | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Colon cancer | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Colorectal cancer | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Malignant melanoma | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Neuroendocrine tumour | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Oesophageal carcinoma | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Prostate cancer | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Rectal cancer | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Squamous cell carcinoma of skin | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Tumour haemorrhage | 5/408 (1.2%) | 5 | 7/202 (3.5%) | 7 | 0/196 (0%) | 0 |
| Tumour pain | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 2 |
| Nervous system disorders | ||||||
| Carotid artery stenosis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Cerebral haemorrhage | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Cerebrovascular accident | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 3/196 (1.5%) | 3 |
| Cerebrovascular disorder | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Loss of consciousness | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Ataxia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Cerebral infarction | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Depressed level of consciousness | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Dizziness | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Encephalopathy | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Ischaemic stroke | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Lethargy | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Seizure | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Subarachnoid haemorrhage | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Syncope | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 3/196 (1.5%) | 3 |
| Transient ischaemic attack | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Product Issues | ||||||
| Device dislocation | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Device occlusion | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Psychiatric disorders | ||||||
| Adjustment disorder | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Mental status changes | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 2/408 (0.5%) | 3 | 1/202 (0.5%) | 1 | 3/196 (1.5%) | 3 |
| Renal failure | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 3/196 (1.5%) | 3 |
| Urinary tract obstruction | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dysphonia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Haemoptysis | 1/408 (0.2%) | 1 | 3/202 (1.5%) | 3 | 1/196 (0.5%) | 1 |
| Laryngeal stenosis | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Pharyngeal oedema | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Pulmonary infarction | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Acute respiratory failure | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Aspiration | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Bronchospasm | 1/408 (0.2%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Chronic obstructive pulmonary disease | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Dyspnoea | 4/408 (1%) | 5 | 3/202 (1.5%) | 3 | 1/196 (0.5%) | 1 |
| Hypoxia | 2/408 (0.5%) | 2 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Interstitial lung disease | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Laryngeal oedema | 5/408 (1.2%) | 5 | 1/202 (0.5%) | 1 | 0/196 (0%) | 0 |
| Lung disorder | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Pleural effusion | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Pneumonia aspiration | 5/408 (1.2%) | 6 | 1/202 (0.5%) | 1 | 4/196 (2%) | 4 |
| Pneumonitis | 7/408 (1.7%) | 9 | 2/202 (1%) | 2 | 1/196 (0.5%) | 2 |
| Pulmonary embolism | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 5/196 (2.6%) | 6 |
| Respiratory distress | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Respiratory failure | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Stridor | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 1/196 (0.5%) | 1 |
| Upper airway obstruction | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 0/408 (0%) | 0 | 2/202 (1%) | 2 | 0/196 (0%) | 0 |
| Skin ulcer | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Pemphigoid | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Psoriasis | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Hypotension | 1/408 (0.2%) | 1 | 1/202 (0.5%) | 1 | 2/196 (1%) | 2 |
| Deep vein thrombosis | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Haemorrhage | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Orthostatic hypotension | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
| Peripheral venous disease | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 0/196 (0%) | 0 |
| Vena cava thrombosis | 0/408 (0%) | 0 | 0/202 (0%) | 0 | 1/196 (0.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 317/408 (77.7%) | 153/202 (75.7%) | 182/196 (92.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 61/408 (15%) | 68 | 22/202 (10.9%) | 26 | 65/196 (33.2%) | 97 |
| Leukopenia | 2/408 (0.5%) | 2 | 2/202 (1%) | 3 | 26/196 (13.3%) | 48 |
| Neutropenia | 2/408 (0.5%) | 2 | 0/202 (0%) | 0 | 63/196 (32.1%) | 103 |
| Thrombocytopenia | 6/408 (1.5%) | 24 | 0/202 (0%) | 0 | 39/196 (19.9%) | 76 |
| Endocrine disorders | ||||||
| Hyperthyroidism | 23/408 (5.6%) | 30 | 6/202 (3%) | 6 | 0/196 (0%) | 0 |
| Hypothyroidism | 68/408 (16.7%) | 79 | 21/202 (10.4%) | 23 | 7/196 (3.6%) | 7 |
| Gastrointestinal disorders | ||||||
| Constipation | 59/408 (14.5%) | 72 | 24/202 (11.9%) | 25 | 54/196 (27.6%) | 68 |
| Diarrhoea | 70/408 (17.2%) | 113 | 15/202 (7.4%) | 20 | 60/196 (30.6%) | 96 |
| Dysphagia | 26/408 (6.4%) | 28 | 8/202 (4%) | 9 | 4/196 (2%) | 4 |
| Nausea | 52/408 (12.7%) | 65 | 13/202 (6.4%) | 14 | 74/196 (37.8%) | 120 |
| Stomatitis | 14/408 (3.4%) | 16 | 6/202 (3%) | 6 | 40/196 (20.4%) | 54 |
| Vomiting | 34/408 (8.3%) | 52 | 8/202 (4%) | 9 | 39/196 (19.9%) | 66 |
| General disorders | ||||||
| Asthenia | 52/408 (12.7%) | 60 | 18/202 (8.9%) | 23 | 38/196 (19.4%) | 61 |
| Fatigue | 66/408 (16.2%) | 74 | 35/202 (17.3%) | 41 | 56/196 (28.6%) | 68 |
| Mucosal inflammation | 15/408 (3.7%) | 16 | 6/202 (3%) | 8 | 43/196 (21.9%) | 58 |
| Pyrexia | 48/408 (11.8%) | 54 | 12/202 (5.9%) | 13 | 21/196 (10.7%) | 33 |
| Infections and infestations | ||||||
| Paronychia | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 21/196 (10.7%) | 24 |
| Pneumonia | 19/408 (4.7%) | 22 | 7/202 (3.5%) | 7 | 10/196 (5.1%) | 12 |
| Investigations | ||||||
| Aspartate aminotransferase increased | 27/408 (6.6%) | 37 | 8/202 (4%) | 10 | 11/196 (5.6%) | 14 |
| Lipase increased | 21/408 (5.1%) | 27 | 5/202 (2.5%) | 8 | 2/196 (1%) | 2 |
| Neutrophil count decreased | 0/408 (0%) | 0 | 1/202 (0.5%) | 1 | 24/196 (12.2%) | 36 |
| Platelet count decreased | 5/408 (1.2%) | 5 | 1/202 (0.5%) | 1 | 22/196 (11.2%) | 47 |
| Weight decreased | 39/408 (9.6%) | 42 | 13/202 (6.4%) | 15 | 26/196 (13.3%) | 32 |
| Alanine aminotransferase increased | 23/408 (5.6%) | 26 | 6/202 (3%) | 6 | 14/196 (7.1%) | 18 |
| Blood creatinine increased | 15/408 (3.7%) | 20 | 3/202 (1.5%) | 4 | 12/196 (6.1%) | 19 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 52/408 (12.7%) | 57 | 20/202 (9.9%) | 22 | 46/196 (23.5%) | 59 |
| Hypocalcaemia | 7/408 (1.7%) | 7 | 0/202 (0%) | 0 | 16/196 (8.2%) | 27 |
| Hypomagnesaemia | 11/408 (2.7%) | 11 | 3/202 (1.5%) | 6 | 45/196 (23%) | 77 |
| Hyponatraemia | 26/408 (6.4%) | 30 | 2/202 (1%) | 4 | 11/196 (5.6%) | 14 |
| Dehydration | 8/408 (2%) | 10 | 0/202 (0%) | 0 | 10/196 (5.1%) | 11 |
| Hyperglycaemia | 29/408 (7.1%) | 37 | 6/202 (3%) | 8 | 8/196 (4.1%) | 10 |
| Hypokalaemia | 21/408 (5.1%) | 26 | 6/202 (3%) | 8 | 22/196 (11.2%) | 42 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 23/408 (5.6%) | 27 | 8/202 (4%) | 8 | 3/196 (1.5%) | 5 |
| Pain in extremity | 5/408 (1.2%) | 6 | 5/202 (2.5%) | 5 | 10/196 (5.1%) | 10 |
| Nervous system disorders | ||||||
| Dizziness | 15/408 (3.7%) | 18 | 7/202 (3.5%) | 7 | 14/196 (7.1%) | 15 |
| Headache | 29/408 (7.1%) | 35 | 11/202 (5.4%) | 12 | 13/196 (6.6%) | 13 |
| Psychiatric disorders | ||||||
| Insomnia | 29/408 (7.1%) | 31 | 8/202 (4%) | 9 | 11/196 (5.6%) | 11 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 44/408 (10.8%) | 47 | 14/202 (6.9%) | 14 | 13/196 (6.6%) | 15 |
| Dyspnoea | 34/408 (8.3%) | 40 | 5/202 (2.5%) | 5 | 18/196 (9.2%) | 21 |
| Productive cough | 19/408 (4.7%) | 22 | 12/202 (5.9%) | 12 | 5/196 (2.6%) | 5 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 3/408 (0.7%) | 3 | 0/202 (0%) | 0 | 11/196 (5.6%) | 11 |
| Dermatitis acneiform | 2/408 (0.5%) | 2 | 2/202 (1%) | 2 | 36/196 (18.4%) | 50 |
| Dry skin | 23/408 (5.6%) | 24 | 4/202 (2%) | 4 | 26/196 (13.3%) | 34 |
| Pruritus | 45/408 (11%) | 61 | 11/202 (5.4%) | 13 | 17/196 (8.7%) | 18 |
| Rash | 50/408 (12.3%) | 62 | 17/202 (8.4%) | 17 | 81/196 (41.3%) | 114 |
| Skin fissures | 1/408 (0.2%) | 1 | 0/202 (0%) | 0 | 18/196 (9.2%) | 23 |
| Vascular disorders | ||||||
| Hypertension | 27/408 (6.6%) | 36 | 9/202 (4.5%) | 10 | 11/196 (5.6%) | 19 |
| Hypotension | 11/408 (2.7%) | 15 | 5/202 (2.5%) | 5 | 11/196 (5.6%) | 16 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Global Clinical Lead |
|---|---|
| Organization | AstraZeneca Clinical Study Information Center |
| Phone | 1-877-240-9479 |
| information.center@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02551159
Other Study ID Numbers:
- D419LC00001
First Posted:
Sep 16, 2015
Last Update Posted:
Oct 13, 2021
Last Verified:
Sep 1, 2021