Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in Combination w/ Tremelimumab Squamous Cell Carcinoma of the Head and Neck

NCT02319044 | Completed Phase 2 Results DMC

• 1 other identifier: D4193C00003
• Study Type: interventional
• Target: 267
• Locations: 15 countries
• Sites: 125

Brief Summary

The purpose of this study is to determine the efficacy and safety of investigational medical products (MEDI4736 monotherapy, tremelimumab monotherapy, and MEDI4736 + tremelimumab combination therapy) in the treatment of patients with recurrent or metastatic carcinoma of the head and neck who have progressed during or after treatment with a platinum containing regimen for recurrent/metastatic disease.

Conditions

Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck

Keywords

Head and neck cancer; SCCHN

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate at 6 Months

  Objective response rate, primary analysis, based on BICR assessments according to RECIST v1.1. The number (%) of patients with a response excludes unconfirmed responses

  After 6 months

• Objective Response Rate at 12 Months

  Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.

  After 12 months

Secondary Outcomes (11)

• Best Objective Response

  After 12 months

• Duration of Response - Participants Remaining in Response

  After 12 months

• Time to Response

  After 12 months

• Time to Onset of Response From First Dose

  After 12 months

• Disease Control Rate (DCR)

  After 6 months

Study Arms (3)

MEDI4736

EXPERIMENTAL

MEDI4736 monotherapy

Drug: MEDI4736

Tremelimumab

EXPERIMENTAL

Tremelimumab monotherapy

Drug: Tremelimumab

MEDI4736 + Tremelimumab

EXPERIMENTAL

MEDI4736 + Tremelimumab combination therapy

Drug: MEDI4736 + Tremelimumab

Interventions

MEDI4736 DRUG

MEDI4736 monotherapy

MEDI4736

Tremelimumab DRUG

Tremelimumab monotherapy

Tremelimumab

MEDI4736 + Tremelimumab DRUG

MEDI4736 + Tremelimumab combination therapy

MEDI4736 + Tremelimumab

Eligibility Criteria

• Age: 18 Years - 96 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years;
• Written informed consent obtained from the patient/legal representative;
• Histologically confirmed recurrent or metastatic SCCHN; tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent; Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible.
• Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
• Confirmed PD-L1-negative SCCHN by Ventana SP263;
• WHO/ECOG performance status of 0 or 1;
• At least 1 measurable lesion at baseline;
• No prior exposure to immune-mediated therapy;
• Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test.

You may not qualify if:

• Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck;
• Received more than 1 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;
• 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;
• another primary malignancy
• Patients with history of brain metastases, spinal cord compression, or a history of leptomeningeal carcinomatosis;
• History of active primary immunodeficiency;
• Known history of previous tuberculosis;
• Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV);

Sponsors & Collaborators

• AstraZeneca: lead
• PRA Health Sciences: collaborator

Study Sites (125)

Research Site

Birmingham, Alabama, 35294, United States

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Yuma, Arizona, 85364, United States

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Little Rock, Arkansas, 72205, United States

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Downey, California, 90241, United States

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Duarte, California, 91010-3012, United States

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La Jolla, California, 92093, United States

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Long Beach, California, 90813, United States

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Los Angeles, California, 90033, United States

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Los Angeles, California, 90095, United States

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San Francisco, California, 94115, United States

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Aurora, Colorado, 80045, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30322, United States

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Augusta, Georgia, 30912, United States

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Macon, Georgia, 31201, United States

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Chicago, Illinois, 60637, United States

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Evanston, Illinois, 60201, United States

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Lexington, Kentucky, 40536-0001, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21204, United States

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Boston, Massachusetts, 02215, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48201, United States

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Southfield, Michigan, 48075, United States

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Rochester, Minnesota, 55905-0001, United States

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St Louis, Missouri, 63110, United States

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Lebanon, New Hampshire, 03756, United States

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New York, New York, 10032, United States

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Stony Brook, New York, 11794, United States

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The Bronx, New York, 10467, United States

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Durham, North Carolina, 27705, United States

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Winston-Salem, North Carolina, 27157, United States

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Portland, Oregon, 97239, United States

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Bethlehem, Pennsylvania, 18015, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Charleston, South Carolina, 29425, United States

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Knoxville, Tennessee, 37909, United States

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Nashville, Tennessee, 37232, United States

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Arlington, Texas, 76012, United States

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Austin, Texas, 78701, United States

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Dallas, Texas, 75230, United States

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Morgantown, West Virginia, 26506, United States

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Milwaukee, Wisconsin, 53226, United States

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Adelaide, 5000, Australia

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Darlinghurst, 2010, Australia

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Tweed Heads, 2485, Australia

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Brussels, 1090, Belgium

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Charleroi, 6000, Belgium

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Kortrijk, 8500, Belgium

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Leuven, 3000, Belgium

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Namur, 5000, Belgium

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Calgary, Alberta, T2N 2T9, Canada

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Moncton, New Brunswick, E1C 6Z8, Canada

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London, Ontario, N6A 4L6, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Olomouc, 775 20, Czechia

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Zlín, 762 75, Czechia

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Angers, 49933, France

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Bordeaux, 33604, France

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Brest, 29229, France

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Dijon, 21079, France

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Le Mans, 72000, France

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Lille, 59020, France

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Lorient, 56322, France

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Lyon, 69373, France

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Montpellier, 34298, France

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Nice, 6189, France

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Rouen, 76038, France

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Saint-Brieuc, 22015, France

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Saint-Grégoire, 35768, France

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Strasbourg, 67085, France

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Toulouse, 31059, France

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Villejuif, 94805, France

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Batumi, 6010, Georgia

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Batumi, 6400, Georgia

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Tbilisi, 0144, Georgia

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Tbilisi, 0177, Georgia

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Tbilisi, 0179, Georgia

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Berlin, 12203, Germany

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Halle, 06120, Germany

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Hanover, 30625, Germany

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Heidelberg, 69120, Germany

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Leipzig, 04103, Germany

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München, 81377, Germany

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Budapest, 1077, Hungary

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Budapest, 1083, Hungary

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Budapest, 1122, Hungary

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Győr, 9024, Hungary

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Gyula, 5700, Hungary

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Kecskemét, 6000, Hungary

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Miskolc, 3526, Hungary

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Zalaegerszeg, 8900, Hungary

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Haifa, 31096, Israel

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Petah Tikva, 4941492, Israel

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Tel Litwinsky, 52621, Israel

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Kuala Lumpur, 59100, Malaysia

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Kuching, 93586, Malaysia

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Daegu, 42601, South Korea

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Goyang-si, 10408, South Korea

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Suwon, 16247, South Korea

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Barakaldo, 48903, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Barcelona, 08907, Spain

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Girona, 17007, Spain

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Granada, 18014, Spain

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Jaén, 23007, Spain

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Madrid, 28041, Spain

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Madrid, 28046, Spain

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Madrid, 28050, Spain

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Marbella (Málaga), 29600, Spain

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Málaga, 29010, Spain

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Valencia, 46014, Spain

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Valencia, 46026, Spain

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Zaragoza, 50009, Spain

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Taipei, 10449, Taiwan

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Aberdeen, AB25 2ZN, United Kingdom

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Birmingham, B15 2TH, United Kingdom

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Glasgow, G12 0YN, United Kingdom

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London, E1 1BB, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

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Related Publications (1)

• Siu LL, Even C, Mesia R, Remenar E, Daste A, Delord JP, Krauss J, Saba NF, Nabell L, Ready NE, Brana I, Kotecki N, Zandberg DP, Gilbert J, Mehanna H, Bonomi M, Jarkowski A, Melillo G, Armstrong JM, Wildsmith S, Fayette J. Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):195-203. doi: 10.1001/jamaoncol.2018.4628.

  PMID: 30383184 DERIVED

Related Links

• Redacted Protocol

MeSH Terms

Conditions

Recurrence; Head and Neck Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms

Results Point of Contact

• Title: Jean Fan, MD, Global Clinical Lead
• Organization: AstraZeneca LP

jean.fan@astrazeneca.com

1-301-398-5080

Study Officials

• Magdalena Wrona

  Medical Scientist AstraZeneca Magdalena.Wrona@astrazeneca.com

  STUDY DIRECTOR

• Lillian Siu, MD

  Princess Margaret Hospital in Toronto, Ontario

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2014
• First Posted: December 18, 2014
• Study Start: April 15, 2015
• Primary Completion: September 26, 2016
• Study Completion: July 6, 2020
• Last Updated: September 29, 2020
• Results First Posted: June 19, 2018

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

IL (3); CZ (2); CA (7); KR (3); TW (1); AU (3); US (43); GE (5); ES (15); BE (5); DE (6); MY (2); GB (6); FR (16); HU (8)