Avelumab (MSB 001718C, BAVENCIO®)

Agent Description

Avelumab is a human IgG1 monoclonal antibody that specifically targets and blocks the ligand (PD-L1) for PD-1. The calculated molecular weight of the molecule is 143 kDa.

Mechanism of Action

PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production. Avelumab binds PD-L1 and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.

Classification

PD-L1 inhibitor

Molecular Targets

PD-L1

Monograph

Avelumab (BAVENCIO®) is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of:

Adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

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.
Patients with locally advanced or metastatic urothelial carcinoma (UC) 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.

In addition to the two FDA approved indications above, avelumab is also being developed both as a monotherapy and in combination with standard treatments in a number of tumor types:

Avelumab monotherapy: Non-small cell lung cancer (NSCLC), Urothelial Carcinoma (UC), Gastric cancer, Merkel cell carcinoma
Avelumab + chemotherapy + radiation therapy: Squamous cell carcinoma of the Head & Neck (SCCHN)
Avelumab + axitinib: Renal cell carcinoma (RCC)

Package insert: https://www.emdserono.com/content/dam/web/corporate/non-images/country-specifics/us/pi/bavencio-pi.pdf

Studies of Interest

Studies that may be supported include:

tumor types not currently under study by the Pharmaceutical Company Collaborator
novel combinations not currently under study by the Pharmaceutical Company Collaborator
studies in relevant patient subpopulations
correlative studies focused on relationships between immune biology and clinical response
early stage studies e.g. neoadjuvant setting, in tumors not currently under study
studies to generate evidence towards further understanding of clinical usefulness of ADCC engagement and the effect on NK population with Avelumab
studies on how to adequately manage immune-related adverse events (irAEs) and infusion-related reactions (IRR)
studies assessing the hypothesis of sequencing PD-L1 with other agents

Studies that would not be supported include:

monotherapy studies
head-to-head studies with other PD-1/PD-L1 drugs
studies of novel dosing and schedules of administration
small under-powered randomized studies
studies that overlap or compete with the EMD Serono development program or where there is compromised or excessive safety risk

Information collaborator would like included in investigator proposals

N/A