Merck KGaA and Pfizer announced the initiation of an international phase III study of the investigational cancer immunotherapy avelumab in a treatment naïve advanced non-small cell lung cancer (NSCLC) setting.

The study, JAVELIN Lung 100, is designed to assess the safety and efficacy of avelumab compared with platinum-based doublet chemotherapy, in patients with late-stage NSCLC who have not previously received any treatment for their systemic lung cancer. Avelumab (previously known as MSB0010718C) is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody that potentially uses the body’s own immune system to fight cancer. By inhibiting PD-L1 interactions, avelumab is thought to potentially enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialise avelumab.

The phase III study is an open-label, multicenter, randomized clinical trial in which patients with recurrent or stage IV PD-L1+ NSCLC will receive either avelumab or the investigator’s choice of platinum-based chemotherapy, depending on the patient’s histology (either squamous or non-squamous), as first-line treatment. Patients will be pre-screened for PD-L1+ status using an immunohistochemistry-based companion diagnostic test.

The study expects to enroll approximately 420 patients across more than 240 sites in Africa, America (North and South), Asia and Europe. Clinical trials in North America on behalf of Merck KGaA, will be conducted by EMD Serono, the company’s US and Canadian biopharma business.

“Through this phase III trial, we hope to gain a better understanding of avelumab as a potential first-line treatment for non-small cell lung cancer – a prevalent and devastating disease,” said Dr. Luciano Rossetti, global head of research & development of the biopharma business of Merck KGaA, Darmstadt, Germany.

“We are working to help patients with this challenging cancer and will continue to develop our NSCLC programme by evaluating avelumab as a potential monotherapy and in combination with our extensive portfolios of approved and investigational oncology therapies.”

The primary endpoint of the study is progression-free survival in patients with PD-L1+ tumours. Secondary endpoints include progression-free survival in patients with strongly PD-L1 positive (PD-L1++) tumours, overall survival, objective response rate, quality of life, tolerability and safety in patients treated with avelumab versus investigator-choice chemotherapy. This is the second randomized phase III study of avelumab in NSCLC initiated in just over six months; the first study was initiated in April 2015 and is evaluating avelumab in patients whose disease has progressed after receiving a platinum-containing doublet chemotherapy compared with docetaxel.

“There is great promise for the use of immunotherapy in the treatment of non-small cell lung cancer and this new trial underscores our continuing commitment to investigating potential immune-based treatment options for this devastating disease,” said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs and chief medical officer for Pfizer Oncology.

“The clinical development programme for avelumab continues to accelerate, and the initiation of this phase III study represents another important achievement in 2015 for the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.”

The clinical development programme for avelumab now includes more than 1,400 patients who have been treated across more than 15 tumour types, including breast cancer, gastric/gastro-esophageal (GEJ) cancers, head and neck cancer, Merkel cell carcinoma, melanoma, NSCLC, ovarian cancer, renal cell carcinoma and urothelial (e.g., bladder) cancer.

Avelumab is the proposed international non-proprietary name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

Globally, lung cancer is the most common cause of cancer-related deaths in men and the second most common in women, responsible for more deaths than colon, breast and prostate cancer combined. NSCLC is the most common type of lung cancer, accounting for 85 to 90 per cent of all lung cancers. The five-year survival rate for people diagnosed with late-stage lung cancer that has spread (metastasized) to other areas of the body is 4 per cent.