Treatment options for patients with non-small-cell lung cancer (NSCLC) have improved in the past decade due to the advent of immune checkpoint inhibitor (ICI) approaches. While NSCLC patients often experience initial responses to ICI, many patients become resistant to the treatment, and the cancer progresses. In such cases, patients may receive chemotherapy in an attempt to control the disease.
A study published last week in the Annals of Oncology gives new hope to some lung cancer patients, particularly those who have become resistant to ICI. The phase 3 randomized study compared standard-of-care chemotherapy to a cancer vaccine called OSE2101. OSE Immunotherapeutics, the company manufacturing OSE2101 released a statement on the same day.
The cancer vaccine OSE2101 represents a type of immunotherapy designed to “educate” the immune system training it to identify and eliminate cancer cells. According to the publication, OSE2101 targets cytotoxic T lymphocytes (CTLs), the immune cells that kill cancer cells. The vaccine specifically induces CTLs to look for specific proteins called tumor-associated antigens (TAAs). TAAs, including HER-2/neu, CEA, MAGE 2, MAGE 3, and p53, are highly expressed on NSCLC cells but rarely found on non-cancerous cells. Thus, OSE2101 instructs CTLs to find and kill cells expressing TAAs, effectively eliminating the cancer.
The trial enrolled patients with NSCLC with specific genetic expression of a protein called human leukocyte antigen-A2 (HLA-A2). All patients had failed prior treatment, including chemotherapy and ICI. The researchers randomized patients 2:1 to OSE2101 or chemotherapy.
The researchers enrolled 219 patients, including 139 who received OSE2101 and 80 who received chemotherapy. Overall, the patients treated with OSE2101 exhibited 14% better overall survival than those treated with chemotherapy.
The researchers also looked specifically at patients with “secondary resistance,” defined as those who initially respond to ICI but then relapse after at least 12 weeks. This represents an important cohort of patients for whom effective treatment options remain lacking. Remarkably, OSE2101 conferred about 41% better overall survival in patients with secondary resistance. In addition, these patients also reported a better quality of life post-treatment than their counterparts receiving standard-of-care therapy.
The authors conclude that OSE2101 presents an efficacious therapeutic option for HLA-A2-positive patients with advanced NSCLC. Particularly, OSE2101 can benefit patients who have developed resistance to immunotherapy.
Sources: J Clin Oncol, Annal Oncol