Clinical trial NCT02369874: Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHN
Keywords: Head and Neck cancer; MEDI4736; Tremelimumab
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-02-24
Enrollment: 736
Sex: ALL
Minimum age (years): 18
Maximum age (years): 96
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: September 2015 to September 2018 (36 months)
Secondary outcomes:
measure: Overall Survival (OS) in PD-L1 Negative Participants
timeFrame: September 2015 to September 2018 (36 months)
measure: Overall Survival (OS) in PD-L1 Positive Participants
timeFrame: September 2015 to September 2018 (36 months)
measure: Progression Free Survival (PFS)
timeFrame: September 2015 to September 2018 (36 months)
measure: Objective Response Rate (ORR)
timeFrame: Assessed at randomization and every 8 weeks thereafter
measure: Duration of Response (DoR)
timeFrame: September 2015 to September 2018 (36 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to 6 months; baseline up to 12 months
measure: Percentage of Participants Alive and Progression Free (APF)
timeFrame: Baseline up to 6 months; baseline up to 12 months
measure: Percentage of Participants Alive
timeFrame: 12, 18 and 24 months
measure: Progression Free Survival (PFS) in PD-L1 Negative Participants
timeFrame: September 2015 to September 2018 (36 months)
measure: Objective Response Rate (ORR) in PD-L1 Negative Participants
timeFrame: September 2015 to September 2018 (36 months)
measure: Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30)
timeFrame: September 2015 to September 2018 (36 months)
measure: 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)
timeFrame: September 2015 to September 2018 (36 months)
measure: Number of Participants Reporting One or More Adverse Events (AE)
timeFrame: First dose to last dose + 90 days or data cut off (up to 36 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Fullerton
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Redondo Beach
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Miami Beach
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Evanston
country: United States
facility: Research Site
state: Illinois
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: McAllen
country: United States
facility: Research Site
state: Texas
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Caba
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Adelaide
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: St Leonards
country: Australia
facility: Research Site
city: Woolloongabba
country: Australia
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Charleroi
country: Belgium
facility: Research Site
city: Kortrijk
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Namur
country: Belgium
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Santo Andre
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Shumen
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Osijek
country: Croatia
facility: Research Site
city: Zagreb
country: Croatia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Zlin
country: Czechia
facility: Research Site
city: Angers
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Le Mans
country: France
facility: Research Site
city: Lyon Cedex 08
country: France
facility: Research Site
city: Montpellier Cedex 5
country: France
facility: Research Site
city: Paris Cedex 5
country: France
facility: Research Site
city: Plerin SUR MER
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: St Grégoire
country: France
facility: Research Site
city: Strasbourg Cedex
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Lorient Cedex
country: Georgia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Potsdam
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Petach-Tikva
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Aosta
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Gallarate
country: Italy
facility: Research Site
city: Legnago
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Hirakata-shi
country: Japan
facility: Research Site
city: Isehara-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kitaadachi-gun
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Nagoya
country: Japan
facility: Research Site
city: Natori-shi
country: Japan
facility: Research Site
city: Okayama
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Osaka
country: Japan
facility: Research Site
city: Sapporo
country: Japan
facility: Research Site
city: Sapporo
country: Japan
facility: Research Site
city: Shimotsuke-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Baia Mare
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Cluj
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Kursk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Sankt-Peterburg
country: Russian Federation
facility: Research Site
city: Sochi
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Vladimir
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Belgrad
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Marbella
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoynan
country: Taiwan
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
Study officials:
affiliation: Medical Director AstraZeneca
name: Nassim Morsli, MD
role: STUDY_DIRECTOR
References:
citation: 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.