Product review: avelumab, an anti-PD-L1 antibody

Abstract

Although immunotherapies have been employed for many decades, immune checkpoint inhibitors have only recently entered the oncologic landscape. Avelumab is a fully human monoclonal antibody that blocks the interaction between PD-L1 on tumor cells and PD-1 on T cells, thereby inhibiting immunosuppression in the tumor microenvironment and reducing tumor growth. Most early clinical trials of avelumab as monotherapy and in combination regimens were part of the international JAVELIN clinical trial program, which included more than 7000 patients in more than 30 trials with at least 15 tumor types. Avelumab has been approved by the U.S. FDA for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma that has progressed during or following treatment with a platinum-based regimen. Its acceptable safety profile and ability to induce durable responses in otherwise deadly tumors provide the rationale for its use in other tumor types and in combination with other therapies.

Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab

“…Moreover, since [ 89 Zr]Zr-DFO-PD-L1 mAb represents the radiolabeled version of avelumab which is currently in clinical trials, this agent could not only serve as a companion diagnostic imaging agent but aid in the drug development process by establishing dosing and then tracing in vivo tissue disposition of avelumab. 50 Although a fluorine-18-labeled small molecule radiotracer would be more desirable for clinical applications, these zirconium-89 labeled FDA-approved therapeutic mAbs are more easily translated into the clinic making possible "proof-of-concept" PET imaging studies earlier in human patients. If these studies prove that PD-L1 has value as a predictive biomarker then this would warrant further development of small molecules or Ab fragments targeting PD-L1 labeled with shorter lived radionuclides (i.e fluorine-18) for clinical applications.…”

Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer

“…[4][5][6][7][8] Among the currently available ICIs, avelumab is a fully human IgG1-isotype anti-PD-L1 mAb, that, therefore, could have potential ADCC properties. 9 In this respect, combined therapy with cetuximab plus avelumab may be able to activate both innate and adaptive immune responses, therefore increasing their antitumour efficacy by the engagement of different types of immune cells. In this respect, the combination of cetuximab plus avelumab with or without chemotherapy is currently in clinical development in several cancers, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and head and neck squamous cell carcinoma (HNSCC).…”

Cell Surface GRP94 as a Novel Emerging Therapeutic Target for Monoclonal Antibody Cancer Therapy

“…However, despite the clinical use of numerous anticancer therapeutic antibodies, a limited number of their therapeutic targets, including CD20, vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), have currently been identified [ 21 , 22 , 23 , 24 , 25 ]. Some examples include ofatumumab, ocrelizumab, ibritumomab tiuxetanand, and rituximab for CD20-targeted mAbs; bevacizumab, ranibizumab, and brolucizumab for VEGF-A-targeted mAbs; cetuximab, panitumumab, and necitumumab for EGFR-targeted mAbs; trastuzumab, and pertuzumab for HER2-targeted mAbs; nivolumab, pembrolizumab, and cemiplimab for PD-1-targeted mAbs; lastly, atezolizumab, avelumab, and durvalumab for PD-L1-targeted mAbs [ 21 , 22 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. As such, identifying novel therapeutic targets and understanding the molecular mechanism of metastatic cancer cells are essential for overcoming unmet medical needs in current cancer therapy.…”