Avelumab is a human monoclonal antibody that targets programmed death-ligand -1 (PD-L1) and is the only PD-L1 antibody with strong “antibody-dependent cell-mediated cytotoxicity (ADCC)” activity. It is also the only PD-L1 antibody with strong “antibody-dependent cell-mediated cytotoxicity (ADCC)” activity. It can play the role of PD-L1 inhibitor to release the suppression of the immune system and restore the anti-tumor activity of T cells, and it can also induce natural killer cells (NK, an important immune cell) to kill cancer cells through ADCC, which is a perfect combination of “attack” and “defense”. The combination of “attack” and “defense” is perfect.
So how does avelumab perform in actual clinical studies for lung cancer? In this article, we will take a look.
First demonstration of the efficacy of avelumab in lung cancer
Avelumab was first approved by the Food and Drug Administration (FDA) in March 2017 to treat metastatic Merkel cell carcinoma, a rare form of skin cancer.
In lung cancer treatment, avelumab is still in its infancy, but there is now a phase Ib study that shows significant efficacy and a good safety profile in advanced lung cancer that is progressive or platinum-resistant.
The JAVELIN study (No. NCT01772004) included patients with metastatic or recurrent non-small cell lung cancer (NSCLC) whose tumors had progressed or were platinum-resistant. The results found that approximately half of the patients had cancer control with avelumab, with 12% achieving definite objective remission and 38% having stable disease.
For safety, the most common treatment-related adverse events were fatigue, infusion-related adverse reactions, and nausea. The incidence of serious adverse events was 13%, with infusion reactions and elevated lipase being the most common.
This study is the first to validate the efficacy and safety of avelumab in platinum-resistant or progressive NSCLC, and provides a basis for its further study in lung cancer.
Avelumab is highly anticipated for lung cancer
In fact, as the fourth approved drug in the PD-1/PD-L1 inhibitor class, the efficacy of avelumab for lung cancer has long been in the spotlight. This is because:
(1) The 3 PD-1/PD-L1 inhibitors (nabumab, pembrolumab, and atezumab) that were marketed before avelumab were all approved for NSCLC because of their excellent clinical outcomes, and avelumab, which is in the same family, likely also has the potential to treat lung cancer.
(2) Avitumumab is the only PD-L1 antibody with strong ADCC activity that not only breaks the immune escape of cancer cells, but also “commands” NK cells to fight them. This theoretical hypothesis has been initially tested in preclinical studies, so investigators expect that avelumab will show stronger anticancer activity than other PD-1/PD-L1 inhibitors in clinical studies.
For the first point, the JAVELIN study has initially confirmed this; for the second point, there are no studies comparing the efficacy of different PD-1/PD-L1 inhibitors, but it is believed that there will be studies in the future to assess which is better or worse.
In addition, it is worth mentioning that in the JAVELIN study, all patients were not distinguished between PD-L1 positivity, meaning that the results of this study apply to all patients with NSCLC.
Study currently underway
A search of the US Clinical Trials Registry showed that in addition to the aforementioned JAVELIN study, there are 17 studies of avelumab alone or in combination for the treatment of cancer, including two studies in patients with lung cancer.
| Table 1. Phase III clinical studies of avelumab for lung cancer (all without results yet) | |||
| Study Population | Trial Status |
Purpose of the study |
|
| NSCLC progressing after platinum-containing dual-agent chemotherapy | On-going, no new patients recruited |
Efficacy and safety of avelumab compared with docetaxel in second-line therapy |
|
| NCT02576574 |
PD-L1-positive, relapsed or advanced NSCLC |
Patients under recruitment |
Efficacy and safety of avelumab compared with platinum-containing double agents in first-line therapy |
Summary
The JAVELIN study has initially suggested that avelumab has a good efficacy and safety profile in platinum-resistant or progressive NSCLC. In addition, two studies in NSCLC have advanced to clinical phase III, and more are underway, so as more data accumulate, avelumab may be licensed for use in lung cancer.