An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.

NCT03084471 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: D4191C00068
• Study Type: interventional
• Target: 867
• Locations: 8 countries
• Sites: 79

Brief Summary

To evaluate the safety, tolerability, and anti-tumor activity of the combination of durvalumab + tremelimumab or durvalumab alone in different solid tumors.

Conditions

Advanced Solid Malignancies

Keywords

Programmed death ligand 1 (PD-L1); Cytotoxic T-lymphocyte antigen-4 (CTLA-4); Durvalumab in combination with tremelimumab

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events of Special Interest (AESIs)

  Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of AESIs were assessed. AESIs included events with a potential inflammatory or immune-mediated mechanism that required interventions such as steroids, immunosuppressants, and/or hormone replacement therapy.

  From screening to safety follow up visit (90 days after last dose), up to approximately 3 years.

Secondary Outcomes (2)

• Overall Survival

  From screening to final data cutoff (maximum up to 4 years) following date of first patient treatment initiation.

• Number of Participants With Adverse Events

  From screening to safety follow up visit (90 days after last dose), maximum up to 4 years.

Study Arms (2)

Combination therapy

EXPERIMENTAL

Combination therapy (durvalumab + tremelimumab) : Patients will receive the combination therapy followed by monotherapy via intravenous (IV) infusion once Q4W: * Durvalumab 1,500 mg + tremelimumab 75 mg on Week 0, for up to a maximum of 4 doses (or cycles) and * Durvalumab 1,500 mg starting 4 weeks after the last infusion of the combination or discontinuation of tremelimumab.

Biological: MEDI4736 (Durvalumab); Biological: MEDI4736 (Durvalumab) + Tremelimumab

Monotherapy

EXPERIMENTAL

Monotherapy (Durvalumab 1,500 mg): Patients will receive durvalumab 1,500 mg via IV infusion Q4W on Week 0.

Biological: MEDI4736 (Durvalumab)

Interventions

MEDI4736 (Durvalumab) BIOLOGICAL

A human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that blocks the interaction of PD-L1 (but not programmed cell death ligand-2) with PD-1 on T cells and CD80 (B7.1) on immune cells (IC).

Combination therapy; Monotherapy

MEDI4736 (Durvalumab) + Tremelimumab BIOLOGICAL

Durvalumab: A human mAb of IgG 1 kappa subclass that blocks the interaction of PD-L1 (but not programmed cell death ligand-2) with PD-1 on T cells and CD80 (B7.1) on IC. Tremelimumab: A human Ig G2 mAb that completely blocks the interaction of human CTLA-4 (cluster of differentiation \[CD\]152) with CD80 and CD86 and increase release of cytokines (interleukin \[IL\]-2 and interferon \[IFN\]-γ) from human T cells, peripheral blood mononuclear cells and whole blood.

Combination therapy

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a life expectancy of at least 12 weeks.
• Age ≥18 years at the time of screening. For patients aged \<20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. For patients aged \<20 years and enrolling in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
• Disease not amenable to curative surgery
• Eastern Cooperative Oncology Group (ECOG) performance status as defined in the specific module.
• Body weight \>30 kg.
• No prior exposure to anti-PD-1 or anti-PD-L1, including on another AstraZeneca study. Exposure to other investigational agents may be permitted after discussion with the Sponsor.
• Adequate organ and marrow function as defined below
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1.0 × 109 /L
• Platelet count ≥75 × 109/L
• Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.
• ALT and AST ≤2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤5 × ULN
• Measured creatinine clearance (CL) \>40 mL/min or calculated creatinine clearance (CL) \>40 mL/min as determined by Cockcroft-Gault (using actual body weight)
• Males:

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Previous IP assignment in the present study.
• Concurrent enrollment in another clinical study, or another sub-study of this protocol, unless it is an observational (non-interventional) clinical study or during the follow up period of an interventional study.
• Participation in another clinical study with an investigational product during the last 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.
• Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
• Local treatment of isolated lesions for palliative intent is acceptable (eg, local surgery or radiotherapy).
• Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product (durvalumab + tremelimumab) and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (79)

Research Site

Santa Rosa, California, 95403, United States

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Washington D.C., District of Columbia, 20007, United States

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Tinley Park, Illinois, 60487, United States

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Omaha, Nebraska, 68130, United States

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Hackensack, New Jersey, 07601, United States

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East Setauket, New York, 11733, United States

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Greenville, South Carolina, 29607, United States

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Knoxville, Tennessee, 37920, United States

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Blacksburg, Virginia, 24060, United States

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Spokane, Washington, 99208, United States

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Moncton, New Brunswick, E1C 6Z8, Canada

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Brampton, Ontario, L6R 3J7, Canada

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Hamilton, Ontario, L8V 5C2, Canada

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Kingston, Ontario, K7L 5P9, Canada

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London, Ontario, N6A 4L6, Canada

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Newmarket, Ontario, L3Y 2P9, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Québec, Quebec, G1R 2J6, Canada

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Besançon, 25030, France

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Bordeaux, 33075, France

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Bordeaux, 33076, France

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Brest, 29609, France

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Dijon, 21034, France

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Lille, 59000, France

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Lyon, 69373, France

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Marseille, 13005, France

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Montpellier, 34298, France

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Nice, 6189, France

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Nîmes, 30029, France

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Paris, 75010, France

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Pierre-Bénite, 69495, France

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Poitiers, 86021, France

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Rouen, 76031, France

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Saint-Herblain, 44805, France

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Strasbourg, 67065, France

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Toulouse, 31059, France

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Tours, 37044, France

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Villejuif, 94805, France

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Berlin, 13585, Germany

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Bielefeld, 33611, Germany

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Dresden, 01307, Germany

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Duisburg, 47179, Germany

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Erlangen, 91054, Germany

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Essen, 45136, Germany

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Gütersloh, 33332, Germany

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Hamburg, 20246, Germany

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Jena, 07747, Germany

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Kiel, 24116, Germany

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Münster, 48149, Germany

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Stuttgart, 70174, Germany

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Würzburg, 97080, Germany

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Ancona, 60126, Italy

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Arezzo, 52100, Italy

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Avellino, 83100, Italy

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Bari, 70124, Italy

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Catania, 95126, Italy

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Lecce, 73100, Italy

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Meldola, 47014, Italy

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Milan, 20141, Italy

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Modena, 41124, Italy

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Padua, 35128, Italy

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Pisa, 56126, Italy

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Ravenna, 48100, Italy

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Roma, 00128, Italy

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Roma, 00152, Italy

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Rozzano, 20089, Italy

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Udine, 33100, Italy

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Leiden, 2333 ZA, Netherlands

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Busan, 49241, South Korea

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Goyang-si, 10408, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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London, EC1A 7BE, United Kingdom

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London, W1G 6AD, United Kingdom

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London, W6 8RF, United Kingdom

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Newcastle, NE7 7DN, United Kingdom

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Sheffield, S10 2SJ, United Kingdom

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Related Publications (1)

• Sonpavde GP, Sternberg CN, Loriot Y, Marabelle A, Lee JL, Flechon A, Roubaud G, Pouessel D, Zagonel V, Calabro F, Banna GL, Shin SJ, Vera-Badillo FE, Powles T, Hellmis E, Miranda PAP, Lima AR, Emeribe U, Oh SM, Hotte SJ. Primary results of STRONG: An open-label, multicenter, phase 3b study of fixed-dose durvalumab monotherapy in previously treated patients with urinary tract carcinoma. Eur J Cancer. 2022 Mar;163:55-65. doi: 10.1016/j.ejca.2021.12.012. Epub 2022 Jan 15.

  PMID: 35042068 DERIVED

Related Links

• redacted\_CSP
• redacted\_SAP

MeSH Terms

Conditions

Diabetes Mellitus, Insulin-Dependent, 12

Interventions

durvalumab; tremelimumab

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical study Information Center

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2017
• First Posted: March 21, 2017
• Study Start: June 5, 2017
• Primary Completion: March 31, 2020
• Study Completion: December 16, 2022
• Last Updated: December 22, 2022
• Results First Posted: June 15, 2021

Record last verified: 2022-12

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

KR (4); NL (1); GB (5); FR (20); CA (10); IT (16); DE (13); US (10)