Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHNPhase 3EAGLENCT02369874
Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer
A Phase 3 study testing MEDI4736 and MEDI4736 + Tremelimumab in people with Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHN, run by AstraZeneca at 168 sites in 24 countries.
Trial summary
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population. Read more about this study
- Who is it for?
- Ages 18 to 96 years
- Conditions the study is for
- Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHN
- What is being tested?
- MEDI4736 and MEDI4736 + Tremelimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 736 participants
- Where
- 168 sitesin 24 countries
- Study dates
- 9 Sep 2015to 13 Nov 2020
- 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 96 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria: - Age ≥18 years; - Written informed consent obtained from the patient/legal representative; - Histologically or cytologically confirmed recurrent or metastatic SCCHN; - Tumor progression or recurrence during or after only one palliative systemic treatment regimen for recurrent or metastatic disease that must have contained a platinum agent OR progression within 6 months of the last dose of platinum given as part of multimodality therapy with curative intent; - Confirmed PD-L1-positive or -negative SCCHN by the Ventana PD-L1 SP263 IHC assay; - WHO/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; At least 1 measurable lesion, - Not previously irradiated; - No prior exposure to immune-mediated therapy; - Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Exclusion Criteria: - Histologically or cytologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck; - Received more than 1 palliative systemic regimen for recurrent or metastatic disease; -Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment; - Receipt of any investigational anticancer therapy within 28 days or 5 half-lives; - Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment; - Major surgical procedure within 28 days prior to the first dose of Investigational Product; - Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion; - Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned Investigational Product; - History of allogeneic organ transplantation; - Active or prior documented autoimmune or inflammatory disorders; - Uncontrolled intercurrent illness; - Patients with a history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis; - Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction; - History of active primary immunodeficiency; - Active tuberculosis; - Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV); - Receipt of live, attenuated vaccine within 30 days prior to the first dose of Investigational Product; - Pregnant or breast-feeding female patients; - Known allergy or hypersensitivity to Investigational Product
Trial locations and contacts
168 sites in 24 countries.
168 sites in 24 countries
United States23 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Boston, Massachusetts, 02215
Research Site
Dallas, Texas, 75230
Research Site
Dallas, Texas, 75246
Research Site
Denver, Colorado, 80218
Research Site
Evanston, Illinois, 60201-1718
Research Site
Fullerton, California, 92835-3825
Research Site
Germantown, Tennessee, 38138
Research Site
Lexington, Kentucky, 40536
Research Site
Los Angeles, California, 90089
Research Site
McAllen, Texas, 78503
Research Site
Miami Beach, Florida, 33140
Research Site
Nashville, Tennessee, 37232
Research Site
Newark, Delaware, 19713
Research Site
Norfolk, Virginia, 23502
Research Site
Orlando, Florida, 32806
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
Redondo Beach, California, 90277
Research Site
Rochester, New York, 14621
Research Site
Rochester, New York, 14642
Research Site
Stanford, California, 94305
Research Site
Tucson, Arizona, 85711
Research Site
Winston-Salem, North Carolina, 27157
Japan21 sites
Research Site
Chūōku, 104-0045
Research Site
Fukuoka, 811-1395
Research Site
Hirakata-shi, 573-1191
Research Site
Isehara-shi, 259-1193
Research Site
Kashiwa, 277-8577
Research Site
Kitaadachi-gun, 362-0806
Research Site
Kobe, 650-0017
Research Site
Kōtoku, 135-8550
Research Site
Matsuyama, 791-0280
Research Site
Nagoya, 464-8681
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
Shimotsuke-shi, 329-0498
Research Site
Sunto-gun, 411-8777
Research Site
Takatsuki-shi, 569-8686
Research Site
Yokohama, 236-0004
Research Site
Yokohama, 241-8515
Russia17 sites
Research Site
Arkhangelsk, 163045
Research Site
Chelyabinsk, 454087
Research Site
Kursk, 305524
Research Site
Moscow, 105229
Research Site
Moscow, 111123
Research Site
Moscow, 125284
Research Site
Moscow, 125367
Research Site
Moscow, 143423
Research Site
Nizhny Novgorod, 603081
Research Site
Omsk, 644013
Research Site
Pyatigorsk, 357502
Research Site
Saint Petersburg, 197758
Research Site
Saint Petersburg, 197785
Research Site
Saint Petersburg, 198255
Research Site
Sochi, 354057
Research Site
Ufa, 450054
Research Site
Vladimir, 600020
France12 sites
Research Site
Angers, 49933
Research Site
Bordeaux, 33000
Research Site
Dijon, 21079
Research Site
Le Mans, 72000
Research Site
Lyon, 69373
Research Site
Montpellier, 34298
Research Site
Paris, 75248
Research Site
Plerin SUR MER, 22190
Research Site
Rouen, 76038
Research Site
Saint-Grégoire, 35768
Research Site
Strasbourg, 67085
Research Site
Villejuif, 94805
Spain12 sites
Research Site
Barcelona, 08035
Research Site
Barcelona, 08036
Research Site
L'Hospitalet de Llobregat, 08908
Research Site
Madrid, 28041
Research Site
Madrid, 28046
Research Site
Madrid, 28050
Research Site
Málaga, 29010
Research Site
Marbella, 29600
Research Site
Pamplona, 31008
Research Site
Valencia, 46014
Research Site
Valencia, 46026
Research Site
Zaragoza, 50009
Italy9 sites
Research Site
Aosta, 11100
Research Site
Bologna, 40138
Research Site
Gallarate, 21013
Research Site
Legnago, 37045
Research Site
Milan, 20133
Research Site
Naples, 80131
Research Site
Pavia, 27100
Research Site
Roma, 00144
Research Site
Siena, 53100
Brazil8 sites
Research Site
Barretos, 14784-400
Research Site
Curitiba, 81520-060
Research Site
Porto Alegre, 90020-090
Research Site
Porto Alegre, 90610-000
Research Site
Rio de Janeiro, 20231-050
Research Site
Santo André, 09060-650
Research Site
São José do Rio Preto, 15090-000
Research Site
São Paulo, 03102-002
Germany8 sites
Research Site
Berlin, 12200
Research Site
Essen, 45122
Research Site
Halle, 06120
Research Site
Hanover, 30625
Research Site
Heidelberg, 69120
Research Site
Leipzig, 04103
Research Site
München, 81377
Research Site
Potsdam, 14467
Belgium6 sites
Research Site
Brussels, 1090
Research Site
Brussels, 1200
Research Site
Charleroi, 6000
Research Site
Kortrijk, 8500
Research Site
Leuven, 3000
Research Site
Namur, 5000
Australia5 sites
Research Site
Adelaide, 5000
Research Site
Heidelberg, 3084
Research Site
Melbourne, 3004
Research Site
St Leonards, 2065
Research Site
Woolloongabba, 4102
Hungary5 sites
Research Site
Budapest, 1083
Research Site
Budapest, 1122
Research Site
Budapest, 1162
Research Site
Győr, 9024
Research Site
Kecskemét, 6000
Israel5 sites
Research Site
Haifa, 31096
Research Site
Jerusalem, 91120
Research Site
Petah Tikva, 49100
Research Site
Tel Aviv, 6423906
Research Site
Tel HaShomer, 52621
Romania5 sites
Research Site
Baia Mare, 430031
Research Site
Brasov, 500152
Research Site
Cluj-Napoca, 400015
Research Site
Cluj-Napoca, 400058
Research Site
Craiova, 200347
South Korea5 sites
Research Site
Daegu, 42601
Research Site
Goyang-si, 10408
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Suwon, 16247
Ukraine5 sites
Research Site
Dnipro, 49102
Research Site
Kyiv, 03115
Research Site
Sumy, 40022
Research Site
Uzhhorod, 88014
Research Site
Zaporizhzhya, 69040
Serbia4 sites
Research Site
Belgrade, 11000
Research Site
Kamenitz, 21204
Research Site
Kragujevac, 34000
Research Site
Niš, 18000
Taiwan4 sites
Research Site
Kaohsiung City, 833
Research Site
Taipei, 100
Research Site
Taipei, 10449
Research Site
Taoynan, 33305
Bulgaria3 sites
Research Site
Shumen, 9700
Research Site
Sofia, 1527
Research Site
Varna, 9000
Poland3 sites
Research Site
Krakow, 31-108
Research Site
Lodz, 93-513
Research Site
Poznan, 60-780
Argentina2 sites
Research Site
CABA, C1426ANZ
Research Site
San Miguel de Tucumán, T4000IAK
About this study
Official title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy and MEDI4736 in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.
Read the detailed description
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.
The main objectives of the study are to:
- assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in patients with squamous cell carcinoma of the head and neck (SCCHN), in terms of overall survival (OS), regardless of PDL-1 status
- assess the efficacy of MEDI4736 monotherapy versus SOC in patients with SCCHN, in terms of OS, regardless of PDL-1 status
Patients will undergo a screening assessment on their tumor tissue sample to determine PD-L1 expression per a pre-specified cut-off level. Patients with ≥25% of tumor cells with membrane staining will be considered PD-L1 positive while those with 0% to 24% of tumor cells with membrane staining will be considered PD-L1 negative. Based on the underlying PD-L1 status, patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 monotherapy, MEDI4736 + tremelimumab combination therapy, or SoC therapy. Patients who discontinue treatment in 1 treatment group may not switch to treatment in a different group.
Stratification factors include PD-L1 status, human papillomavirus status, (in patients with oropharyngeal cancer only), and smoking status.
Tumor assessments will be performed every 8 weeks until objective tumor response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
- Being tested
- MEDI4736, MEDI4736 + Tremelimumab, Standard of Care
- Keywords
- Head and Neck cancer; MEDI4736; Tremelimumab
- Medical subject headings
- Recurrence, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4736Drug
MEDI4736 Monotherapy
MEDI4736 + TremelimumabDrug
MEDI4736 + Tremelimumab combination therapy
Standard of CareDrug
Standard of Care
| Study group | Role | What they receive |
|---|---|---|
| MEDI4736 | Experimental | MEDI4736 monotherapy Receives: Drug: MEDI4736 |
| MEDI4736 + Tremelimumab | Experimental | MEDI4736 + tremelimumab combination therapy Receives: Drug: MEDI4736 + Tremelimumab |
| Standard of Care | Active comparator | Standard of Care Receives: Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause. OS was analyzed for the full analysis set, regardless of programmed death-ligand 1 (PD-L1) status.
Measured: September 2015 to September 2018 (36 months)
Secondary outcomes (13)
Overall Survival (OS) in PD-L1 Negative Participants
OS is defined as the time from the date of randomization until death due to any cause. PD-L1 negative was defined as <25% of tumor cells with membrane staining for PD-L1 at any intensity.
Measured: September 2015 to September 2018 (36 months)
Overall Survival (OS) in PD-L1 Positive Participants
OS is defined as the time from the date of randomization until death due to any cause. PD-L1 positive was defined as ≥25% of tumor cells with membrane staining for PD-L1 at any intensity.
Measured: September 2015 to September 2018 (36 months)
Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization until the date of objective disease progression or death based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: September 2015 to September 2018 (36 months)
Objective Response Rate (ORR)
The percentage of participants who experienced an objective response (complete response [CR] or partial response [PR]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Measured: Assessed at randomization and every 8 weeks thereafter
Duration of Response (DoR)
Median DoR, in months, based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A complete response was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A partial response was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Measured: September 2015 to September 2018 (36 months)
Disease Control Rate (DCR)
6 Months: The percentage of participants who had a best objective response of complete response (CR) or partial response (PR) in the first 6 months or had demonstrated stable disease (SD) for a minimum interval of 24 weeks following randomization.
12 Months: The percentage of participants who had a best objective response of CR or PR within 12 months or had demonstrated SD for a minimum interval of 48 weeks following randomization.
Objective response was based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Measured: Baseline up to 6 months; baseline up to 12 months
Percentage of Participants Alive and Progression Free (APF)
APF is defined as the percentage of participants who are alive and progression free at 6 months and 12 months after randomization. Estimates of progression free survival were based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Baseline up to 6 months; baseline up to 12 months
Percentage of Participants Alive
Percentage of participants alive at 12, 18 and 24 months using a Kaplan Meier estimate.
Measured: 12, 18 and 24 months
Progression Free Survival (PFS) in PD-L1 Negative Participants
Number of participants with confirmed objective disease progression (PD) at the time of the participant's last evaluable response evaluation criteria in solid tumors 1.1 (RECIST1.1) assessment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD-L1 negative was defined as <25% of tumor cells with membrane staining for PD-L1 at any intensity.
Measured: September 2015 to September 2018 (36 months)
Objective Response Rate (ORR) in PD-L1 Negative Participants
The percentage of PD-L1 negative participants who experienced an objective response (complete response [CR] or partial response [PR]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. PD-L1 negative was defined as <25% of tumor cells with membrane staining for PD-L1 at any intensity.
Measured: September 2015 to September 2018 (36 months)
Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30)
The EORTC QLQ-C30 consists of 30 questions that can be combined to produce functional scales (e.g. physical), symptom scales (e.g. fatigue), and a global measure of health status. Each of the scales are measured from 0 to 100. Deterioration was defined as a 10-point decrease from baseline in a functioning or global health status/ quality of life score or a 10-point increase from baseline in a symptom score.
Measured: September 2015 to September 2018 (36 months)
Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35)
The EORTC QLQ-H\&N35 comprises of 35 questions to assess head and neck cancer symptoms (e.g. pain, swallowing). Deterioration was defined as a 10-point increase from baseline in the symptom score.
Measured: September 2015 to September 2018 (36 months)
Number of Participants Reporting One or More Adverse Events (AE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Inclusive of AEs and serious AEs.
Measured: First dose to last dose + 90 days or data cut off (up to 36 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2015 (estimated)
- Study start9 Sep 2015
- Primary completion10 Sep 2018
- Study completion13 Nov 2020
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 (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHNStudies 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
- 736 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nassim Morsli, MD, Study director, Medical Director AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02369874
- Sponsor's protocol ID
- D4193C00002
- Acronym
- EAGLE
- Status last verified
- Jan 2021
- First submitted
- 18 Feb 2015
- Last updated
- 10 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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.
Publications
Ferris RL, Haddad R, Even C, Tahara M, Dvorkin M, Ciuleanu TE, Clement PM, Mesia R, Kutukova S, Zholudeva L, Daste A, Caballero-Daroqui J, Keam B, Vynnychenko I, Lafond C, Shetty J, Mann H, Fan J, Wildsmith S, Morsli N, Fayette J, Licitra L. Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study. Ann Oncol. 2020 Jul;31(7):942-950. doi: 10.1016/j.annonc.2020.04.001. Epub 2020 Apr 12.
PubMed 32294530
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 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 Monotherapy and MEDI4736 in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
- ClinicalTrials.gov ID
- NCT02369874
- Acronym / sponsor ID
- EAGLE / D4193C00002
- Keywords
- Head and Neck cancer; MEDI4736; Tremelimumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 736 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 9 Sep 2015 (actual)
- Primary completion
- 10 Sep 2018 (actual)
- Study completion
- 13 Nov 2020 (actual)
- First posted
- 24 Feb 2015 (estimated)
- Results
- Posted 3 Oct 2019
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, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.
Detailed description
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.
The main objectives of the study are to:
- assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in patients with squamous cell carcinoma of the head and neck (SCCHN), in terms of overall survival (OS), regardless of PDL-1 status
- assess the efficacy of MEDI4736 monotherapy versus SOC in patients with SCCHN, in terms of OS, regardless of PDL-1 status
Patients will undergo a screening assessment on their tumor tissue sample to determine PD-L1 expression per a pre-specified cut-off level. Patients with ≥25% of tumor cells with membrane staining will be considered PD-L1 positive while those with 0% to 24% of tumor cells with membrane staining will be considered PD-L1 negative. Based on the underlying PD-L1 status, patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 monotherapy, MEDI4736 + tremelimumab combination therapy, or SoC therapy. Patients who discontinue treatment in 1 treatment group may not switch to treatment in a different group.
Stratification factors include PD-L1 status, human papillomavirus status, (in patients with oropharyngeal cancer only), and smoking status.
Tumor assessments will be performed every 8 weeks until objective tumor response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MEDI4736 | Experimental | Drug: MEDI4736MEDI4736 monotherapy |
| MEDI4736 + Tremelimumab | Experimental | Drug: MEDI4736 + TremelimumabMEDI4736 + tremelimumab combination therapy |
| Standard of Care | Active comparator | Drug: Standard of CareStandard of Care |
Who may qualify
- Ages
- 18 to 96 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| MEDI4736MEDI4736 Monotherapy | Drug | MEDI4736 |
| MEDI4736 + TremelimumabMEDI4736 + Tremelimumab combination therapy | Drug | MEDI4736 + Tremelimumab |
| Standard of CareStandard of Care | Drug | Standard of Care |
Primary outcome
Overall Survival (OS)
Time frame: September 2015 to September 2018 (36 months)
OS is defined as the time from the date of randomization until death due to any cause. OS was analyzed for the full analysis set, regardless of programmed death-ligand 1 (PD-L1) status.
13 secondary outcomes
Overall Survival (OS) in PD-L1 Negative Participants
Time frame: September 2015 to September 2018 (36 months)
Overall Survival (OS) in PD-L1 Positive Participants
Time frame: September 2015 to September 2018 (36 months)
Progression Free Survival (PFS)
Time frame: September 2015 to September 2018 (36 months)
Objective Response Rate (ORR)
Time frame: Assessed at randomization and every 8 weeks thereafter
Duration of Response (DoR)
Time frame: September 2015 to September 2018 (36 months)
Disease Control Rate (DCR)
Time frame: Baseline up to 6 months; baseline up to 12 months
Percentage of Participants Alive and Progression Free (APF)
Time frame: Baseline up to 6 months; baseline up to 12 months
Percentage of Participants Alive
Time frame: 12, 18 and 24 months
Progression Free Survival (PFS) in PD-L1 Negative Participants
Time frame: September 2015 to September 2018 (36 months)
Objective Response Rate (ORR) in PD-L1 Negative Participants
Time frame: September 2015 to September 2018 (36 months)
Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30)
Time frame: September 2015 to September 2018 (36 months)
Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35)
Time frame: September 2015 to September 2018 (36 months)
Number of Participants Reporting One or More Adverse Events (AE)
Time frame: First dose to last dose + 90 days or data cut off (up to 36 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32294530Ferris RL, Haddad R, Even C, Tahara M, Dvorkin M, Ciuleanu TE, Clement PM, Mesia R, Kutukova S, Zholudeva L, Daste A, Caballero-Daroqui J, Keam B, Vynnychenko I, Lafond C, Shetty J, Mann H, Fan J, Wildsmith S, Morsli N, Fayette J, Licitra L. Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study. Ann Oncol. 2020 Jul;31(7):942-950. doi: 10.1016/j.annonc.2020.04.001. Epub 2020 Apr 12.
- AstraZeneca Cancer Study Locator Service Phone: 877 400 4656 Email: astrazeneca@emergingmed.comLink 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.
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.
Nassim Morsli, MD study director
Medical Director AstraZeneca
168 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MEDI4736 and MEDI4736 + Tremelimumab in people with Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHN, run by AstraZeneca at 168 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 10 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 168 sites in United States, Japan, Russia, France, Spain and 19 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 3 Oct 2019). 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) (time frame: September 2015 to September 2018 (36 months)). 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 NCT02369874, which also lists 1 linked publication.
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 10 Feb 2021.