Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer

NCT ID: NCT02369874

Last Updated: 2021-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 736 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-09
• Study Completion Date: 2020-11-13

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).

Conditions

Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHN

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MEDI4736

MEDI4736 monotherapy

Group Type: EXPERIMENTAL

MEDI4736

Intervention Type: DRUG

MEDI4736 Monotherapy

MEDI4736 + Tremelimumab

MEDI4736 + tremelimumab combination therapy

Group Type: EXPERIMENTAL

MEDI4736 + Tremelimumab

Intervention Type: DRUG

MEDI4736 + Tremelimumab combination therapy

Standard of Care

Standard of Care

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

Standard of Care

Interventions

MEDI4736

MEDI4736 Monotherapy

Intervention Type: DRUG

MEDI4736 + Tremelimumab

MEDI4736 + Tremelimumab combination therapy

Intervention Type: DRUG

Standard of Care

Standard of Care

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 96 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nassim Morsli, MD

Role: STUDY_DIRECTOR

Medical Director AstraZeneca

Locations

Research Site

Tucson, Arizona, United States

Research Site

Fullerton, California, United States

Research Site

Los Angeles, California, United States

Research Site

Redondo Beach, California, United States

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Stanford, California, United States

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Denver, Colorado, United States

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Newark, Delaware, United States

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Miami Beach, Florida, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Evanston, Illinois, United States

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Lexington, Kentucky, United States

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Boston, Massachusetts, United States

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Rochester, New York, United States

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Rochester, New York, United States

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Winston-Salem, North Carolina, United States

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Pittsburgh, Pennsylvania, United States

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Germantown, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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McAllen, Texas, United States

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Norfolk, Virginia, United States

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CABA, , Argentina

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San Miguel de Tucumán, , Argentina

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Adelaide, , Australia

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Heidelberg, , Australia

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Melbourne, , Australia

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St Leonards, , Australia

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Woolloongabba, , Australia

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Brussels, , Belgium

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Brussels, , Belgium

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Charleroi, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Namur, , Belgium

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Barretos, , Brazil

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Curitiba, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Santo André, , Brazil

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São José do Rio Preto, , Brazil

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São Paulo, , Brazil

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Shumen, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Temuco, , Chile

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Osijek, , Croatia

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Zagreb, , Croatia

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Olomouc, , Czechia

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Zlín, , Czechia

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Angers, , France

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Bordeaux, , France

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Dijon, , France

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Le Mans, , France

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Lyon, , France

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Montpellier, , France

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Paris, , France

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Plerin SUR MER, , France

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Rouen, , France

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Saint-Grégoire, , France

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Strasbourg, , France

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Villejuif, , France

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Lorient Cedex, , Georgia

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Berlin, , Germany

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Essen, , Germany

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Halle, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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München, , Germany

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Potsdam, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Győr, , Hungary

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Kecskemét, , Hungary

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Haifa, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Tel Aviv, , Israel

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Tel Litwinsky, , Israel

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Aosta, , Italy

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Bologna, , Italy

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Gallarate, , Italy

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Legnago, , Italy

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Milan, , Italy

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Napoli, , Italy

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Pavia, , Italy

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Roma, , Italy

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Siena, , Italy

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Chūōku, , Japan

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Fukuoka, , Japan

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Hirakata-shi, , Japan

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Isehara-shi, , Japan

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Kashiwa, , Japan

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Kitaadachi-gun, , Japan

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Kobe, , Japan

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Kōtoku, , Japan

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Matsuyama, , Japan

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Nagoya, , Japan

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Natori-shi, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Sapporo, , Japan

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Sapporo, , Japan

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Sayama, , Japan

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Shimotsuke-shi, , Japan

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Sunto-gun, , Japan

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Takatsuki-shi, , Japan

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Yokohama, , Japan

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Yokohama, , Japan

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Krakow, , Poland

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Lodz, , Poland

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Poznan, , Poland

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Baia Mare, , Romania

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Brasov, , Romania

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Cluj-Napoca, , Romania

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Cluj-Napoca, , Romania

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Craiova, , Romania

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Arkhangelsk, , Russia

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Chelyabinsk, , Russia

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Kursk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Omsk, , Russia

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Pyatigorsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Sochi, , Russia

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Ufa, , Russia

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Vladimir, , Russia

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Belgrade, , Serbia

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Kamenitz, , Serbia

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Kragujevac, , Serbia

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Niš, , Serbia

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Daegu, , South Korea

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Goyang-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Barcelona, , Spain

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Barcelona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Marbella, , Spain

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Málaga, , Spain

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Pamplona, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Kaohsiung City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoynan, , Taiwan

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Dnipro, , Ukraine

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Kyiv, , Ukraine

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Sumy, , Ukraine

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Uzhhorod, , Ukraine

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Zaporizhzhia, , Ukraine

Countries

United States; Argentina; Australia; Belgium; Brazil; Bulgaria; Chile; Croatia; Czechia; France; Georgia; Germany; Hungary; Israel; Italy; Japan; Poland; Romania; Russia; Serbia; South Korea; Spain; Taiwan; Ukraine

References

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.

Reference Type: DERIVED

PMID: 32294530 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

http://www.emergingmed.com/networks/AstraZeneca

AstraZeneca Cancer Study Locator Service Phone: 877 400 4656 Email: astrazeneca@emergingmed.com

Other Identifiers

D4193C00002

Identifier Type: -

Identifier Source: org_study_id