Squamous Cell Carcinoma of the Head and NeckPhase 3KESTRELNCT02551159
Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer
A Phase 3 study testing MEDI4736, Tremelimumab and MEDI4736+Tremelimumab in people with Squamous Cell Carcinoma of the Head and Neck, run by AstraZeneca at 197 sites in 23 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- MEDI4736, Tremelimumab and MEDI4736+Tremelimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 823 participants
- Where
- 197 sitesin 23 countries
- Study dates
- 15 Oct 2015to 21 May 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
Who cannot join
- 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
Trial locations and contacts
197 sites in 23 countries.
197 sites in 23 countries
Japan20 sites
Research Site
Akashi-shi, 673-8558
Research Site
Chiba, 260-8717
Research Site
Fukuoka, 811-1347
Research Site
Hirakata-shi, 573-1191
Research Site
Isehara-shi, 259-1193
Research Site
Kagoshima, 890-8520
Research Site
Kanazawa, 920-8650
Research Site
Kitaadachi-gun, 362-0806
Research Site
Kobe, 650-0017
Research Site
Kōtoku, 135-8550
Research Site
Natori-shi, 981-1293
Research Site
Okayama, 700-8558
Research Site
Osaka, 541-8567
Research Site
Sapporo, 003-0804
Research Site
Sapporo, 060-8648
Research Site
Sayama, 589-8511
Research Site
Sunto-gun, 411-8777
Research Site
Takatsuki-shi, 569-8686
Research Site
Toyoake-shi, 470-1192
Research Site
Yokohama, 241-8515
United States19 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Aurora, Colorado, 80045
Research Site
Baltimore, Maryland, 21201
Research Site
Baltimore, Maryland, 21231
Research Site
Boston, Massachusetts, 02215
Research Site
Chapel Hill, North Carolina, 27599
Research Site
Charlotte, North Carolina, 28204
Research Site
Chicago, Illinois, 60637
Research Site
Cleveland, Ohio, 44115
Research Site
Columbus, Ohio, 43210
Research Site
Fort Myers, Florida, 33916
Research Site
Morristown, New Jersey, 07960
Research Site
Nashville, Tennessee, 37203
Research Site
New York, New York, 10029
Research Site
New York, New York, 10065
Research Site
St. Petersburg, Florida, 33705
Research Site
Tampa, Florida, 33612
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Winston-Salem, North Carolina, 27157
Brazil13 sites
Research Site
Barretos, 14784-400
Research Site
Curitiba, 81520-060
Research Site
Florianópolis, 88034-000
Research Site
Ijuí, 98700-000
Research Site
Porto Alegre, 90035-003
Research Site
Porto Alegre, 90619-900
Research Site
Porto Alegre, 91350-200
Research Site
Recife, 50040-000
Research Site
Rio de Janeiro, 22793-080
Research Site
Santo André, 09060-650
Research Site
Santo André, 09080-110
Research Site
São José do Rio Preto, 15090-000
Research Site
São Paulo, 03102-002
Spain13 sites
Research Site
Badajoz, 06008
Research Site
Barcelona, 08035
Research Site
Barcelona, 08036
Research Site
Jaén, 23007
Research Site
L'Hospitalet de Llobregat, 08907
Research Site
Madrid, 28007
Research Site
Madrid, 28034
Research Site
Madrid, 28040
Research Site
Madrid, 28050
Research Site
Málaga, 29010
Research Site
Marbella, 29600
Research Site
Valencia, 46026
Research Site
Zaragoza, 50009
Russia12 sites
Research Site
Arkhangelsk, 163045
Research Site
Krasnodar, 350040
Research Site
Moscow, 125367
Research Site
Obninsk, 249036
Research Site
Omsk, 644013
Research Site
Saint Petersburg, 191014
Research Site
Saint Petersburg, 195271
Research Site
Saint Petersburg, 197758
Research Site
Saint Petersburg, 198255
Research Site
Sochi, 354057
Research Site
Ufa, 450054
Research Site
Yekaterinburg, 620905
Ukraine11 sites
Research Site
Dnipro, 49102
Research Site
Ivano-Frankivsk, 76018
Research Site
Kapitanivka Village, 08111
Research Site
Kharkiv Region, 61070
Research Site
Kirovohrad, 25006
Research Site
Kryvyi Rih, 50048
Research Site
Kyiv, 03022
Research Site
Kyiv, 03115
Research Site
Odesa, 65055
Research Site
Sumy, 40022
Research Site
Vinnytsia, 21029
France10 sites
Research Site
Bordeaux, 33000
Research Site
Brest, 29200
Research Site
Dijon, 21079
Research Site
Lyon, 69373
Research Site
Nice, 06100
Research Site
Paris, 75015
Research Site
Poitiers, 86021
Research Site
Toulouse, 31059
Research Site
Vandœuvre-lès-Nancy, 54519
Research Site
Villejuif, 94800
Germany10 sites
Research Site
Berlin, 12203
Research Site
Erlangen, 91054
Research Site
Essen, 45147
Research Site
Frankfurt am Main, 60590
Research Site
Freiburg im Breisgau, 79106
Research Site
Hamburg, 20246
Research Site
Heidelberg, 69120
Research Site
Mainz, 55131
Research Site
Tübingen, 72076
Research Site
Würzburg, 97070
Poland10 sites
Research Site
Bialystok, 15-027
Research Site
Bielsko-Biala, 43-300
Research Site
Gdansk, 80-214
Research Site
Gdynia, 81-519
Research Site
Lodz, 93-513
Research Site
Lublin, 20-090
Research Site
Poznan, 60-780
Research Site
Poznan, 61-866
Research Site
Szczecin, 71-730
Research Site
Warsaw, 02-781
South Korea10 sites
Research Site
Cheongju-si, 28644
Research Site
Hwasun-gun, 58128
Research Site
Incheon, 21565
Research Site
Seogu, 49241
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 135-710
Research Site
Suwon, 16499
Canada9 sites
Research Site
Calgary, Alberta, T2N 4N2
Research Site
Halifax, Nova Scotia, B3H 1V7
Research Site
Hamilton, Ontario, L8V 5C2
Research Site
London, Ontario, N6A 4L6
Research Site
Moncton, New Brunswick, E1C 8X3
Research Site
Montreal, Quebec, H4A 3J1
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Winnipeg, Manitoba, R3E 0V9
Italy9 sites
Research Site
Cona, 44124
Research Site
Florence, 50134
Research Site
Messina, 98158
Research Site
Milan, 20133
Research Site
Padova, 35128
Research Site
Palermo, 90127
Research Site
Salerno, 84131
Research Site
Siena, 53100
Research Site
Torino, 10126
India7 sites
Research Site
Bangalore, 560027
Research Site
Bangalore, 560076
Research Site
Bengaluru, 560076
Research Site
Gūrgaon, 122001
Research Site
Karamsad, 388325
Research Site
Madurai, 625107
Research Site
Pune, 411001
Taiwan7 sites
Research Site
Kaohsiung City
Research Site
Taichung, 40447
Research Site
Taichung, 40705
Research Site
Tainan, 704
Research Site
Taipei, 100
Research Site
Taipei, 10449
Research Site
Taipei, 11217
United Kingdom7 sites
Research Site
Bebington, CH63 4JY
Research Site
Birmingham, B15 2TT
Research Site
London, EC1A 7BE
Research Site
London, SW3 6JJ
Research Site
Manchester, M20 4BX
Research Site
Sutton, SM2 5PT
Research Site
Taunton, TA1 5DA
Greece6 sites
Research Site
Athens, 115 22
Research Site
Athens, 11527
Research Site
Athens, 124 61
Research Site
Athens, 18547
Research Site
Heraklion, 711 11
Research Site
Thessaloniki, 54645
Belgium5 sites
Research Site
Brussels, 1000
Research Site
Brussels, 1090
Research Site
Brussels, 1200
Research Site
Leuven, 3000
Research Site
Namur, 5000
Thailand5 sites
Research Site
Bangkok, 10330
Research Site
Bangkok, 10700
Research Site
Chiang Mai, 50200
Research Site
Hat Yai, 90110
Research Site
Pathum Thani, 12120
Austria4 sites
Research Site
Graz, 8036
Research Site
Innsbruck, 6020
Research Site
Linz, 4010
Research Site
Vienna, 1140
Vietnam4 sites
Research Site
Hà Nội, 100000
Research Site
Hanoi, 100000
Research Site
Hanoi
Research Site
Ho Chi Minh City, 700000
Philippines3 sites
Research Site
Cebu City, 6000
Research Site
Las Piñas, 1740
Research Site
Quezon City, 1112
About this study
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
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.
Read the 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.
- Being tested
- MEDI4736, Tremelimumab, MEDI4736+Tremelimumab, Cetuximab, 5-fluorouracil (5FU)
- Keywords
- programmed cell death ligand 1 (PD-L1), MEDI4736, Cytotoxic T-lymphocyte-associated antigen 4 {CTLA-4}, PFS, SCCHN
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4736Biological
Anti-PD-L1 antibody
TremelimumabBiological
Anti-CTLA-4 Antibody
MEDI4736+TremelimumabBiological
CetuximabBiological
Monoclonal Antibody
5-fluorouracil (5FU)Drug
Chemotherapy Agent
CisplatinDrug
Chemotherapy agent
CarboplatinDrug
Chemotherapy Agent
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy | Experimental | MEDI4736 monotherapy. Receives: Biological: MEDI4736 |
| Combination Therapy | Experimental | MEDI4736+Tremelimumab combination therapy Receives: Biological: Tremelimumab; Biological: MEDI4736+Tremelimumab |
| Standard of Care | Active comparator | Standard of Care treatment Receives: Biological: Cetuximab; Drug: 5-fluorouracil (5FU); Drug: Cisplatin; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)
Number of participants with Overall Survival (OS)
Measured: From date of randomization until time of final analysis, an average of approximately 4 years
Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup
Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
Measured: From date of randomization until time of final analysis, an average of approximately 4 years
Secondary outcomes (11)
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)
Number of participants with Overall Survival (OS)
Measured: From date of randomization until time of final analysis, an average of approximately 4 years
Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup
Percentage of patients alive
Measured: 12, 18 and 24 months after randomization
Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup
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
Measured: 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
Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup
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)
Measured: 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
Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Measured: 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
Overall Survival (OS) Status in the All-comers (Full Analysis Set)
Number of participants with Overall Survival (OS)
Measured: From date of randomization until time of final analysis, an average of approximately 4 years
Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)
Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
Measured: From date of randomization until time of final analysis, an average of approximately 4 years
Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)
Percentage of patients alive
Measured: 12, 18 and 24 months after randomization
Progression Free Survival (PFS) in the All-comers (Full Analysis Set)
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
Measured: 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
Objective Response Rate (ORR) in the All-comers (Full Analysis Set)
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)
Measured: 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
Duration of Response (DoR) in the All-comers (Full Analysis Set)
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2015 (estimated)
- Study start15 Oct 2015
- Primary completion6 Jul 2020
- Study completion21 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 823 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Olsson, Study directorTanguy Seiwert, Principal investigator, The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02551159
- Sponsor's protocol ID
- D419LC00001
- Acronym
- KESTREL
- Status last verified
- Sep 2021
- First submitted
- 9 Sep 2015
- Last updated
- 13 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Seiwert TY, Wildsmith S, Fayette J, Harrington K, Gillison M, Ahn MJ, Takahashi S, Weiss J, Machiels JP, Baxi S, Baker V, Evans B, Morsli N, Jill Walker, Real K, L'Hernault A, Psyrri A. Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2024 Mar 2;73(4):70. doi: 10.1007/s00262-024-03643-3.
PubMed 38430375Hwang M, Seiwert TY. Are taxanes the future for head and neck cancer? Pragmatism in the immunotherapy era. Lancet Oncol. 2021 Apr;22(4):413-415. doi: 10.1016/S1470-2045(21)00121-2. Epub 2021 Mar 5. No abstract available.
PubMed 33684371
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02551159
- Acronym / sponsor ID
- KESTREL / D419LC00001
- Keywords
- programmed cell death ligand 1 (PD-L1), MEDI4736, Cytotoxic T-lymphocyte-associated antigen 4 {CTLA-4}, PFS, SCCHN
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 823 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2015 (actual)
- Primary completion
- 6 Jul 2020 (actual)
- Study completion
- 21 May 2021 (actual)
- First posted
- 16 Sep 2015 (estimated)
- Results
- Posted 13 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Monotherapy | Experimental | Biological: MEDI4736MEDI4736 monotherapy. |
| Combination Therapy | Experimental | Biological: Tremelimumab, Biological: MEDI4736+TremelimumabMEDI4736+Tremelimumab combination therapy |
| Standard of Care | Active comparator | Biological: Cetuximab, Drug: 5-fluorouracil (5FU), Drug: Cisplatin, Drug: CarboplatinStandard of Care treatment |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI4736Anti-PD-L1 antibody | Biological | Monotherapy |
| TremelimumabAnti-CTLA-4 Antibody | Biological | Combination Therapy |
| MEDI4736+Tremelimumab | Biological | Combination Therapy |
| CetuximabMonoclonal Antibody | Biological | Standard of Care |
| 5-fluorouracil (5FU)Chemotherapy Agent | Drug | Standard of Care |
| CisplatinChemotherapy agent | Drug | Standard of Care |
| CarboplatinChemotherapy Agent | Drug | Standard of Care |
Primary outcome
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)
Time frame: 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
Time frame: 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)
11 secondary outcomes
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup
Time frame: 12, 18 and 24 months after randomization
Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup
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
Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup
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
Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup
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
Overall Survival (OS) Status in the All-comers (Full Analysis Set)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)
Time frame: 12, 18 and 24 months after randomization
Progression Free Survival (PFS) in the All-comers (Full Analysis Set)
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
Objective Response Rate (ORR) in the All-comers (Full Analysis Set)
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
Duration of Response (DoR) in the All-comers (Full Analysis Set)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38430375Seiwert TY, Wildsmith S, Fayette J, Harrington K, Gillison M, Ahn MJ, Takahashi S, Weiss J, Machiels JP, Baxi S, Baker V, Evans B, Morsli N, Jill Walker, Real K, L'Hernault A, Psyrri A. Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2024 Mar 2;73(4):70. doi: 10.1007/s00262-024-03643-3.
- Derived from this study: PubMed 33684371Hwang M, Seiwert TY. Are taxanes the future for head and neck cancer? Pragmatism in the immunotherapy era. Lancet Oncol. 2021 Apr;22(4):413-415. doi: 10.1016/S1470-2045(21)00121-2. Epub 2021 Mar 5. No abstract available.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Olsson study director
Tanguy Seiwert principal investigator
The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
197 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MEDI4736, Tremelimumab and MEDI4736+Tremelimumab in people with Squamous Cell Carcinoma of the Head and Neck, run by AstraZeneca at 197 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 197 sites in Japan, United States, Brazil, Spain, Russia and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) (time frame: From date of randomization until time of final analysis, an average of approximately 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02551159, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2021.