Personalized Neoantigen Vaccine and Durvalumab in ES-SCLC

Summary: 

Small cell lung cancer (SCLC) is an aggressive type of lung cancer that accounts for up to 15% of all new diagnoses of lung cancers. Each year, over 30,000 new patients will be diagnosed with SCLC in the United States. Treatment for patients with extensive stage SCLC, disease that has spread beyond the chest, includes chemotherapy with roughly 67% of patients initially responding. However, on average, patients relapse and succumb to their disease within 4 months. Studies looking into adding immune checkpoint inhibitors (ICIs) to SCLC treatment have had limited success, thus, new treatment strategies are urgently needed. One strategy is the utilization of a personalized vaccine that uses neoantigens to train the immune cells to recognize SCLC cells. Neoantigens are new proteins that form on cancer cells when certain mutations occur in tumor DNA. This will ensure the vaccine is tailored to the recipient’s particular disease and unique cancer mutations. This phase II study will assess the safety of the combination of durvalumab, an ICI that targets PD-L1 and prevents cancer cells from hiding from immune cells, in combination with a personalized neoantigen vaccine in patients with extended stage SCLC. Patients will receive standard of care chemotherapy and durvalumab, while a vaccine is being created using the patient’s own cancer cells. Once developed, the patient will receive the personalized vaccine in combination with durvalumab. The combination of the two drugs will synergize together to enhance the immune system’s ability to target SCLC cells. To the researchers’ knowledge, this is the only ongoing trial of a personalized neoantigen vaccine that is integrated into first-line therapy in SCLC.

Trial Registration: ClinicalTrials.gov Identifier: NCT04397003