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NCT02551159: KESTREL

Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer

Completed Phase 3 Results posted Last updated 13 October 2021
What this trial tests

Phase 3 trial testing MEDI4736 in Squamous Cell Carcinoma of the Head and Neck in 823 participants. Completed in 21 May 2021.

Timeline
15 October 2015
Primary endpoint
6 July 2020
21 May 2021

Quick facts

Lead sponsorAstraZeneca
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment823
Start date15 October 2015
Primary completion6 July 2020
Estimated completion21 May 2021
Sites197 locations across Italy, Japan, Taiwan, Vietnam, Poland, South Korea, Philippines, Russia

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Squamous Cell Carcinoma of the Head and Neck. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) Primary · From date of randomization until time of final analysis, an average of approximately 4 years

Number of participants with Overall Survival (OS)

GroupValue95% CI
Durvalumab + Tremelimumab162
Durvalumab84
Standard of Care (SOC)77
Durvalumab + Tremelimumab1
Durvalumab1
Standard of Care (SOC)3
Durvalumab + Tremelimumab27
Durvalumab14
Standard of Care (SOC)14
Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup Primary · 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)

GroupValue95% CI
Durvalumab + Tremelimumab11.29.5 – 13.9
Durvalumab10.99.0 – 14.3
Standard of Care (SOC)10.98.3 – 13.4
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC) Secondary · From date of randomization until time of final analysis, an average of approximately 4 years

Number of participants with Overall Survival (OS)

GroupValue95% CI
Durvalumab + Tremelimumab162
Durvalumab84
Standard of Care (SOC)77
Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup Secondary · 12, 18 and 24 months after randomization

Percentage of patients alive

at 12 months
GroupValue95% CI
Durvalumab + Tremelimumab49.342.0 – 56.2
Durvalumab48.037.8 – 57.4
Standard of Care (SOC)44.033.6 – 53.8
at 18 months
GroupValue95% CI
Durvalumab + Tremelimumab31.825.3 – 38.5
Durvalumab34.725.5 – 44.1
Standard of Care (SOC)30.821.6 – 40.4
at 24 months
GroupValue95% CI
Durvalumab + Tremelimumab23.918.0 – 30.1
Durvalumab27.619.2 – 36.6
Standard of Care (SOC)26.417.8 – 35.7
Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup Secondary · 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

GroupValue95% CI
Durvalumab + Tremelimumab2.82.6 – 3.3
Durvalumab2.81.7 – 4.2
Standard of Care (SOC)5.34.3 – 5.8
Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup Secondary · 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)

GroupValue95% CI
Durvalumab + Tremelimumab48
Durvalumab16
Standard of Care (SOC)47
Durvalumab + Tremelimumab142
Durvalumab83
Standard of Care (SOC)47
Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup Secondary · 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

GroupValue95% CI
Durvalumab + Tremelimumab6.54.5 – 16.1
Durvalumab12.35.6 – NA
Standard of Care (SOC)4.23.0 – 5.7
Overall Survival (OS) Status in the All-comers (Full Analysis Set) Secondary · From date of randomization until time of final analysis, an average of approximately 4 years

Number of participants with Overall Survival (OS)

GroupValue95% CI
Durvalumab + Tremelimumab356
Durvalumab176
Standard of Care (SOC)171
Durvalumab + Tremelimumab4
Durvalumab3
Standard of Care (SOC)6
Durvalumab + Tremelimumab53
Durvalumab25
Standard of Care (SOC)29
Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set) Secondary · 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)

GroupValue95% CI
Durvalumab + Tremelimumab10.79.6 – 12.2
Durvalumab9.98.9 – 11.9
Standard of Care (SOC)10.39.0 – 12.1
Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) Secondary · 12, 18 and 24 months after randomization

Percentage of patients alive

at 12 months
GroupValue95% CI
Durvalumab + Tremelimumab46.541.6 – 51.2
Durvalumab42.835.9 – 49.5
Standard of Care (SOC)43.836.8 – 50.5
at 18 months
GroupValue95% CI
Durvalumab + Tremelimumab30.726.3 – 35.2
Durvalumab31.224.9 – 37.7
Standard of Care (SOC)29.723.5 – 36.1
at 24 months
GroupValue95% CI
Durvalumab + Tremelimumab22.918.9 – 27.0
Durvalumab24.718.9 – 30.8
Standard of Care (SOC)23.217.6 – 29.2
Progression Free Survival (PFS) in the All-comers (Full Analysis Set) Secondary · 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

GroupValue95% CI
Durvalumab + Tremelimumab2.82.6 – 2.9
Durvalumab2.82.0 – 2.8
Standard of Care (SOC)5.44.4 – 5.7
Objective Response Rate (ORR) in the All-comers (Full Analysis Set) Secondary · 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)

GroupValue95% CI
Durvalumab + Tremelimumab90
Durvalumab35
Standard of Care (SOC)101
Durvalumab + Tremelimumab323
Durvalumab169
Standard of Care (SOC)105

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Durvalumab + Tremelimumab
Serious: 168/408 (41%)
Deaths: 356/413
Durvalumab
Serious: 78/202 (39%)
Deaths: 176/204
Standard of Care (SOC)
Serious: 94/196 (48%)
Deaths: 171/206

Serious adverse events (234 terms)

ReactionSystemDurvalumab + TremelimumabDurvalumabStandard of Care (SOC)
PneumoniaInfections and infestations
DiarrhoeaGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Tumour haemorrhageNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumonitisRespiratory, thoracic and mediastinal disorders
DysphagiaGastrointestinal disorders
PyrexiaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
InfectionInfections and infestations
Respiratory tract infectionInfections and infestations
SepsisInfections and infestations
Laryngeal oedemaRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
ColitisGastrointestinal disorders
DeathGeneral disorders
Mucosal inflammationGeneral disorders
LeukopeniaBlood and lymphatic system disorders
Lower respiratory tract infectionInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Other adverse events (48 terms — click to expand)

ReactionSystemDurvalumab + TremelimumabDurvalumabStandard of Care (SOC)
RashSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
HypothyroidismEndocrine disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
AstheniaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
PyrexiaGeneral disorders
HypomagnesaemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Mucosal inflammationGeneral disorders
StomatitisGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Weight decreasedInvestigations
Dermatitis acneiformSkin and subcutaneous tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
HyperglycaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Aspartate aminotransferase increasedInvestigations
HypertensionVascular disorders
LeukopeniaBlood and lymphatic system disorders
DysphagiaGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
Dry skinSkin and subcutaneous tissue disorders
Neutrophil count decreasedInvestigations
HyperthyroidismEndocrine disorders
Back painMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
ParonychiaInfections and infestations
Lipase increasedInvestigations
PneumoniaInfections and infestations
Productive coughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pneumonia, Diarrhoea, Febrile neutropenia, Vomiting, Tumour haemorrhage, Pneumonitis, Dysphagia, Pyrexia.

Data from ClinicalTrials.gov NCT02551159 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  2. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC).
    Cohen EEW, Bell RB, Bifulco CB, Burtness B, et al · · 2019 · cited 528× · PMID 31307547 · DOI 10.1186/s40425-019-0662-5
  3. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  4. Immunotherapy for head and neck cancer: Recent advances and future directions.
    Cramer JD, Burtness B, Ferris RL. · · 2019 · cited 238× · PMID 31683169 · DOI 10.1016/j.oraloncology.2019.104460
  5. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
    Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3
  6. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  7. Antibodies to watch in 2017.
    Reichert JM. · · 2017 · cited 194× · PMID 27960628 · DOI 10.1080/19420862.2016.1269580
  8. Antibodies to watch in 2018.
    Kaplon H, Reichert JM. · · 2018 · cited 179× · PMID 29300693 · DOI 10.1080/19420862.2018.1415671

Verify or expand the search:

Other trials of MEDI4736

Trials testing the same drug.

Other recruiting trials for Squamous Cell Carcinoma of the Head and Neck

Currently open trials in the same condition.

Other AstraZeneca trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02551159.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing