Symptoms and General Pathology

All Conditions

Death

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Immunoglobulin G

Interferons

Immunoglobulins, Intravenous

Tremelimumab

Antineoplastic Agents, Immunological

Immunologic Factors

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.

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

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)

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.

MEDI4736 (Durvalumab) + Tremelimumab

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

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

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

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

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.

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.

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

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

AstraZeneca

All participants received fixed-dose of durvalumab 1500 mg every 4 weeks until disease progression or unacceptable toxicity.

Age, Continuous

Sex: Female, Male

Race was not a mandatory variable to be collected in some sites due to data privacy reasons. Hence, the total number of participants analysed for race is lesser than Overall (Safety Analysis Set)

Race (NIH/OMB)

Global Clinical Lead

Any adverse event (AE)

Any AE of common terminology criteria for AEs Grade 3 or 4

Any serious adverse event (SAE) (including events with outcome = death)

Any AE with outcome = death

Any AE, causally related to treatment

Any AE of common terminology criteria Grade 3 or 4, causally related to treatment

Any SAE, causally related to treatment

Any AE with outcome = death, causally related to treatment

Any AE leading to discontinuation of study treatment

Event outcome resolved

Event outcome not resolved

AESIs are defined as AEs with a likely inflammatory or immune-mediated pathophysiological basis, resulting from the mechanism of action of durvalumab and/or tremelimumab and requiring more frequent monitoring and/or interventions, such as corticosteroids, immunosuppressants, and/or endocrine therapy.

AESI

AEPIs are defined as AEs that could have a potential inflammatory or immune-mediated pathophysiological basis, resulting from the mechanism of action of durvalumab but are more likely to have occurred due to other pathophysiological mechanisms, thus, the likelihood of the event being inflammatory or immune-mediated in nature is not high and/or is most often or usually explained by the other causes.

AEPI

The imAEs that occurred during this study were determined by a programmatic algorithm that required specific treatment for AESIs to be considered imAEs; the same specific treatment was required for AEPIs as well.

imAE

Safety analysis set: all enrolled participants who received at least one dose of durvalumab.

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

Safety analysis set: all enrolled participants who received at least 1 dose of durvalumab.

Spots Global Cancer Trial Database for medi4736 (durvalumab) + tremelimumab