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Advanced Solid MalignanciesPhase 3STRONGNCT03084471

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

A Phase 3 study testing MEDI4736 (Durvalumab) and MEDI4736 (Durvalumab) + Tremelimumab in people with Advanced Solid Malignancies, run by AstraZeneca at 79 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 to 130 years
Conditions the study is for
Advanced Solid Malignancies
What is being tested?
MEDI4736 (Durvalumab) and MEDI4736 (Durvalumab) + Tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
867 participants
Where
79 sitesin 8 countries
Study dates
5 Jun 2017to 16 Dec 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • Creatinine CL = Weight (kg) × (140 - Age) (mL/min) 72 × serum creatinine (mg/dL)
  • Females:
  • Creatinine CL = Weight (kg) × (140 - Age) x 0.85 (mL/min) 72 × serum creatinine (mg/dL)
  • Female patients of childbearing potential (ie, not surgically sterile or post menopausal) who are sexually active with a non sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy (see Section 3.8 and specifically Table 1).
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test (per Section 4) for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle- stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Non sterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy.

Who cannot join

  • 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).
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  • 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
  • History of leptomeningeal carcinomatosis
  • Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on baseline brain imaging (please refer to RECIST for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least 4 weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10 mg/day of prednisone or its equivalent and anti-convulsants for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
  • History of active primary immunodeficiency.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
  • Known allergy or hypersensitivity to study drug(s) or compounds of similar biologic composition to the study drug(s), or any of the study drug excipients.
  • Any unresolved NCI CTCAE Grade ≥2 toxicities from prior anti cancer therapy with the exception of vitiligo, alopecia, and the laboratory values defined in the inclusion criteria.
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician
  • For women only, currently pregnant (confirmed with positive pregnancy test) or breast feeding.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy.
  • Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.

Trial locations and contacts

79 sites in 8 countries.

79 sites in 8 countries

France20 sites

  • Research Site

    Besançon, 25030

  • Research Site

    Bordeaux, 33075

  • Research Site

    Bordeaux, 33076

  • Research Site

    Brest, 29609

  • Research Site

    Dijon, 21034

  • Research Site

    Lille, 59000

  • Research Site

    Lyon, 69373

  • Research Site

    Marseille, 13005

  • Research Site

    Montpellier, 34298

  • Research Site

    Nice, 6189

  • Research Site

    Nîmes, 30029

  • Research Site

    Paris, 75010

  • Research Site

    Pierre-Bénite, 69495

  • Research Site

    Poitiers, 86021

  • Research Site

    Rouen, 76031

  • Research Site

    Saint-Herblain, 44805

  • Research Site

    Strasbourg, 67065

  • Research Site

    Toulouse, 31059

  • Research Site

    Tours, 37044

  • Research Site

    Villejuif, 94805

Other trials in France

Italy16 sites

  • Research Site

    Ancona, 60126

  • Research Site

    Arezzo, 52100

  • Research Site

    Avellino, 83100

  • Research Site

    Bari, 70124

  • Research Site

    Catania, 95126

  • Research Site

    Lecce, 73100

  • Research Site

    Meldola, 47014

  • Research Site

    Milan, 20141

  • Research Site

    Modena, 41124

  • Research Site

    Padova, 35128

  • Research Site

    Pisa, 56126

  • Research Site

    Ravenna, 48100

  • Research Site

    Roma, 00128

  • Research Site

    Roma, 00152

  • Research Site

    Rozzano, 20089

  • Research Site

    Udine, 33100

Other trials in Italy

Germany13 sites

  • Research Site

    Berlin, 13585

  • Research Site

    Bielefeld, 33611

  • Research Site

    Dresden, 01307

  • Research Site

    Duisburg, 47179

  • Research Site

    Erlangen, 91054

  • Research Site

    Essen, 45136

  • Research Site

    Gütersloh, 33332

  • Research Site

    Hamburg, 20246

  • Research Site

    Jena, 07747

  • Research Site

    Kiel, 24116

  • Research Site

    Münster, 48149

  • Research Site

    Stuttgart, 70174

  • Research Site

    Würzburg, 97080

Other trials in Germany

United States10 sites

  • Research Site

    Blacksburg, Virginia, 24060

  • Research Site

    East Setauket, New York, 11733

  • Research Site

    Greenville, South Carolina, 29607

  • Research Site

    Hackensack, New Jersey, 07601

  • Research Site

    Knoxville, Tennessee, 37920

  • Research Site

    Omaha, Nebraska, 68130

  • Research Site

    Santa Rosa, California, 95403

  • Research Site

    Spokane, Washington, 99208

  • Research Site

    Tinley Park, Illinois, 60487

  • Research Site

    Washington D.C., District of Columbia, 20007

Other trials in United States

Canada10 sites

  • Research Site

    Brampton, Ontario, L6R 3J7

  • Research Site

    Greenfield Park, Quebec, J4V 2H1

  • Research Site

    Hamilton, Ontario, L8V 5C2

  • Research Site

    Kingston, Ontario, K7L 5P9

  • Research Site

    London, Ontario, N6A 4L6

  • Research Site

    Moncton, New Brunswick, E1C 6Z8

  • Research Site

    Newmarket, Ontario, L3Y 2P9

  • Research Site

    Québec, Quebec, G1R 2J6

  • Research Site

    Toronto, Ontario, M4N 3M5

  • Research Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

United Kingdom5 sites

  • Research Site

    London, EC1A 7BE

  • Research Site

    London, W1G 6AD

  • Research Site

    London, W6 8RF

  • Research Site

    Newcastle, NE7 7DN

  • Research Site

    Sheffield, S10 2SJ

Other trials in United Kingdom

South Korea4 sites

  • Research Site

    Busan, 49241

  • Research Site

    Goyang-si, 10408

  • Research Site

    Seoul, 03722

  • Research Site

    Seoul, 05505

Other trials in South Korea

Netherlands1 site

  • Research Site

    Leiden, 2333 ZA

Other trials in Netherlands

About this study

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

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

Read the detailed description

This is an open-label, multi-center, study to determine the short and long term safety of fixed doses of durvalumab 1500 mg + tremelimumab 75 mg combination therapy or durvalumab 1500 mg monotherapy in patients with advanced solid malignancies. This study is modular in design, one or more of the modules will be opened in a given country / region based on local patient population prevalence, and results of feasibility studies. The total number of patients to be enrolled overall and in each module will depend on the types and number of tumor modules added to the main study and country-specific ancillary studies. The number of patients and sites to be involved in individual countries will be dependent on each module or ancillary study. This study consisted of a screening period, a treatment period, a 90 day safety follow-up period and a survival follow-up period. Patients will receive the investigation product (IP) via intravenous (IV) infusion once every 4 weeks (Q4W) in combination therapy or monotherapy as mentioned below - Combination therapy: Durvalumab 1,500 mg + tremelimumab 75 mg on Week 0, for up to a maximum of 4 doses (or cycles) followed by durvalumab 1,500 mg starting 4 weeks after the last infusion of the combination or discontinuation of tremelimumab.

Monotherapy: Durvalumab 1,500 mg on week 0.

Patients will attend a safety follow-up visit 90 days after study treatment discontinuation. Thereafter, patients will be contacted by phone or electronic communication every 3 months for survival status up to 5 years following date of first patient treatment initiation. All patients will be followed for a minimum of 6 months following enrolment of last patient. It is anticipated that the total enrolment period for the overall study will be approximately 2 to 3 years, with an overall duration of approximately 5 years

Being tested
MEDI4736 (Durvalumab), MEDI4736 (Durvalumab) + Tremelimumab
Keywords
Programmed death ligand 1 (PD-L1), Cytotoxic T-lymphocyte antigen-4 (CTLA-4), Durvalumab in combination with tremelimumab
Medical subject headings
Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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).

  • MEDI4736 (Durvalumab) + TremelimumabBiological

    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.

Study groups in NCT03084471
Study groupRoleWhat they receive
Combination therapyExperimentalCombination 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.
Receives: Biological: MEDI4736 (Durvalumab); Biological: MEDI4736 (Durvalumab) + Tremelimumab
MonotherapyExperimentalMonotherapy (Durvalumab 1,500 mg): Patients will receive durvalumab 1,500 mg via IV infusion Q4W on Week 0.
Receives: Biological: MEDI4736 (Durvalumab)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (2)

  1. Overall Survival

    Overall survival was defined as the time from the first date of treatment until death due to any cause.

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

  2. Number of Participants With Adverse Events

    Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of treatment-emergent AEs (including SAEs) will be assessed

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2017
  2. Study start5 Jun 2017
  3. Primary completion31 Mar 2020
  4. Study completion16 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
867 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03084471
Sponsor's protocol ID
D4191C00068
Acronym
STRONG
Status last verified
Dec 2022
First submitted
7 Mar 2017
Last updated
22 Dec 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Publications

  • 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.

    PubMed 35042068

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MEDI4736 (Durvalumab) and MEDI4736 (Durvalumab) + Tremelimumab in people with Advanced Solid Malignancies, run by AstraZeneca at 79 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 79 sites in France, Italy, Germany, United States, Canada and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events of Special Interest (AESIs) (time frame: From screening to safety follow up visit (90 days after last dose), up to approximately 3 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03084471, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2022.

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