Tremelimumab (CP-675,206)

Agent Description

Human immunoglobulin IgG2 monoclonal antibody specific for human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4; CD152), a cell surface receptor that is expressed primarily on activated T cells.

Mechanism of Action

Anti-CTLA4 monoclonal antibody that blocks the inhibitory signal resulting from CTLA-4 binding to CD80/86, leading to prolongation and enhancement of T-cell activation and expansion.

Classification

Anti-CTLA4 monoclonal antibody; immunotherapeutic

Molecular Target

CTLA4

Monograph

CTLA-4 is expressed exclusively on the surface of T cells. CTLA-4 serves to inhibit T-cell activation through delivery of inhibitory signals and through ligand competition with the co-stimulatory receptor, CD28. Inhibition of CTLA-4 can shift the balance of signaling in the immune system in favor of greater T-cell activation, engendering a greater immune response and potentially resulting in the rejection of tumor by the host's immune system.

Tremelimumab is an investigational anti-CTLA-4 monoclonal antibody being clinically evaluated in combination therapy for the potential treatment of cancer.

Studies of Interest

Areas of interest:

Priority will be given to proposals that advance understanding of core development programs in NSCLC, Bladder and HNSCC. Only Tremelimumab + Durvalumab combination proposals will be considered.

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 tremelimumab + durvalumab combination therapy.
Non-small Cell Lung Cancer:
- Tremelimumab + durvalumab in patients excluded from the registration program (un-resectable Stage IIIA/IIIB and Stage IV)
- Tremelimumab + durvalumab combinations with chemotherapy, radiotherapy or other agents (immunotherapy/targeted therapies)
- Patient reported outcomes and patient experience of patients receiving tremelimumab + durvalumab
Urothelial Cancer:
- Tremelimumab + durvalumab combined with SoC chemotherapy in front-line metastatic urothelial cancer
- Tremelimumab + durvalumab combined with novel agents or radiotherapy in front-line or relapsed bladder cancer
- Optimal utilization of tremelimumab + durvalumab in non-muscle invasive bladder cancer
- Tremelimumab + durvalumab combined with SoC chemotherapy, novel agents, or radiotherapy in patients with stage II-IV non-metastatic disease
- Patient reported outcomes and experience of patients receiving tremelimumab + durvalumab in bladder cancer
Head & Neck Cancer:
- Tremelimumab + durvalumab in HNSCC patients excluded from the registration programs
- Tremelimumab + durvalumab in locally advanced HNSCC sub-populations
- Tremelimumab + durvalumab combined with targeted agents (e.g. cetuximab, AZ targeted small molecules etc.), radiotherapy and/or chemotherapy
- Patient reported outcomes and experience of patients receiving tremelimumab + durvalumab in HNSCC

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
Single agent tremelimumab or combination proposals other than with durvalumab

Information collaborator would like included in investigator proposals

N/A