Durvalumab (MEDI4736, IMFINZI™)

Agent Description

Immuno-modulator; a human monoclonal antibody of the immunoglobulin G1 kappa (IgG1κ) subclass that inhibits binding of Programmed Death Ligand 1 (PD-L1) to PD-1 and CD80.

Mechanism of Action

Selective, high affinity antibody that blocks PD-L1 binding to PD-1 and CD80, allowing T cells to recognize and kill tumor cells.

Classification

PD-L1 blocking monoclonal antibody

Molecular Targets

PD-L1 and CD80

Monograph

Durvalumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:

have disease progression during or following platinum-containing chemotherapy
have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

There are multiple monotherapy and combination clinical trials ongoing with durvalumab.

Package insert: https://www.azpicentral.com/imfinzi/imfinzi.pdf#page=1

Studies of Interest

Areas of interest:

Priority will be given to proposals that advance understanding of core development programs in NSCLC, Bladder and HNSCC.

The following should be used as general guidance:

Translationally focused proposals that are designed to gain insight into mechanisms of intrinsic or acquired resistance to durvalumab monotherapy or durvalumab + tremelimumab combination therapy.
Non-small Cell Lung Cancer:
- Durvalumab +/- tremelimumab in patients excluded from the registration program (un-resectable Stage IIIA/IIIB and Stage IV)
- Durvalumab-based combinations in immunotherapy pre-treated patients
- Durvalumab +/- tremelimumab combinations with chemotherapy, radiotherapy or other agents (immunotherapy/targeted therapies)
- Enhance biomarker knowledge to support clinical decision making for durvalumab-based combinations
- Early predictors of clinical activity and immune-related adverse events
- Patient reported outcomes and patient experience of patients receiving durvalumab +/- tremelimumab
Urothelial Cancer:
- Durvalumab +/- tremelimumab combined with SoC chemotherapy in front-line metastatic urothelial cancer
- Durvalumab +/- tremelimumab combined with novel agents or radiotherapy in front-line or relapsed bladder cancer
- Optimal utilization of durvalumab +/- tremelimumab in non-muscle invasive bladder cancer
- Durvalumab +/- tremelimumab combined with SoC chemotherapy, novel agents, or radiotherapy in patients with stage II-IV non-metastatic disease
- Real-world evidence (RWE) on treatment patterns and outcomes with introduction of checkpoint inhibitors in bladder cancer
- Prognostic value of PD-L1 expression in patients with bladder cancer treated with the SOC
- Patient reported outcomes and experience of patients receiving durvalumab +/- tremelimumab in bladder cancer
Head & Neck Cancer:
- Durvalumab +/- tremelimumab in HNSCC patients excluded from the registration programs
- Durvalumab +/- tremelimumab in locally advanced HNSCC sub-populations
- Durvalumab +/- tremelimumab combined with targeted agents (e.g. cetuximab, AZ targeted small molecules etc.), radiotherapy and/or chemotherapy
- Patient reported outcomes and experience of patients receiving durvalumab +/- tremelimumab in HNSCC
- Generate data in historical recurrent/metastatic HNSCC cohorts based on biomarkers and current SoCs
Other indications (e.g. SCLC, GI tumors) supported by robust preclinical data may be considered.
Pre-clinical studies will be considered

Areas NOT of interest:

Studies that overlap or compete with AstraZeneca development program or where there is compromised or excessive safety risk will not be accepted

Information collaborator would like included in investigator proposals

N/A