Lung cancer is the second most common cancer in both men and women (excluding skin cancer). It is the leading cause of cancer death with one in four cancer deaths attributed to lung cancer. About 80 to 85% of lung cancers are non-small cell lung cancer (NSCLC), while the remaining 10-15% are small cell lung cancer (SCLC). Depending on the stage of cancer, the treatment options include surgery, radiofrequency ablation (RFA), radiation therapy, chemotherapy, targeted therapies and immunotherapy.
Merck KGaA, Darmstadt, Germany, and Pfizer have formed a strategic alliance to co-develop and co-commercialize the drug PF-06439535 as a potential biosimilar to bevacizumab (Avastin), a recombinant humanized monoclonal immunoglobulin G1 antibody used in the treatment of non-squamous non-small cell lung cancer.
PF-06439535, also known as Avelumab or MSB0010718C is a fully human anti-PD-L1 (programmed cell death protein-1 ligand) monoclonal antibody which blocks the interaction of PD1 on immune cells with PD-L1 on tumour cells, mediating the ADCC (antibody-dependent cell-mediated cytotoxicity) lysis of tumour cells.
Merck and Pfizer are expecting to launch avelumab commercially in 2017. They have initiated 6 pivotal clinical trials for this drug in 2015. These include trials for NSCLC first line/second line, ovarian platinum resistant/refractory, gastric first line/third line, bladder first line therapy and more than 20 clinical programs across various tumour indications.
Avelumab has received a breakthrough therapy designation by the U.S FDA for metastatic Merkel cell carcinoma for patients who have completed at least one course of chemotherapy. It has also been granted the fast track designation and orphan drug designation by the FDA.
The clinical trial program for the study of avelumab in the treatment of multiple types of cancer is known as the JAVELIN series. The study for lung cancer is termed as JAVELIN Lung 200 and is presently in Phase III. JAVELIN Lung 200 is a global, randomised, open-label phase III trial aimed at demonstrating superiority of avelumab versus docetaxel in subjects with PD-L1 positive, NSCLC after failure of a platinum-based doublet. The study is designed to be completed in 2023, with an estimated 750 patients from more than 30 countries participating in the study.
Data from another phase Ib trial (JAVELIN Solid Tumour trial) evaluating avelumab as first-line therapy in patients with metastatic NSCLC were recently presented at the American Society of Clinical Oncology Annual Meeting held in Chicago, Illinois, from June 3 – 7, 2016. Patients with advanced NSCLC not previously treated for metastatic or recurrent disease and not selected for PDL-1 expression were treated with avelumab 10 mg/kg intravenously twice weekly until progression, unacceptable toxicity or withdrawal. In 145 patients followed for 13 weeks, treatment-related adverse events (TRAE) occurred in 56.6% (82 patients) and Grade ≥ 3 TRAEs were reported in 13 pts (9.0%). There were no treatment-related deaths. Among 75 pts with more than 3 months of follow up, unconfirmed objective response rate (ORR) was 18.7% (95% CI: 10.6, 29.3). Stable disease was observed in 34 pts (45.3%); the disease control rate was 64.0%. PD-L1 expression was evaluable in 60% of the patients.
Results showed the drug to have an acceptable safety profile and clinical activity with a suggested trend of higher objective response rate (ORR) in PD-L1 positive tumors.
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Credit: Dr. Neha on behalf of Borderless Access
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