CheckMate 9LA – Investigating the role of immunotherapy combinations in patients with non-small cell lung cancer

Martin Reck | Aug 2020 | ASCO20 Virtual | Onkologi /hematologi |

Martin Reck
MD, Ph.D.,
Head of the Department
of Thoracic Oncology
at the Lung Clinic
Grosshansdorf, Germany

CheckMate 9LA is the second trial in a row of trials investigating the role of immunotherapy combinations in patients with non-small cell lung cancer (NSCLC). At the preplanned interim analysis after 8.1 months, overall survival was significantly prolonged with the combination of ipilimumab (IPI) and nivolumab (NIVO) and chemo vs chemo alone as front-line therapy in unselected patients with advanced NSCLC at all PD-L1 levels. CheckMate 9LA1 is the second trial in a row of trials investigating the role of immunotherapy combinations in patients with non-small cell lung cancer (NSCLC). In this article I will present the results of a preplanned interim analysis, including the study’s background, method, endpoints, results and challenges. An innovative combination of chemotherapy and immunotherapy The purpose of CheckMate 9LA was to investigate if the survival rate of NSCLC could be improved by combining a limited amount of chemotherapy (two cycles) with the immunotherapy combination studied in CheckMate 227.2 CheckMate 227 investigated the efficacy of the combination of ipilimumab (IPI) and nivolumab (NIVO). This combination showed an improved overall survival and durability of response compared to chemo in first-line advanced NSCLC –regardless of PD-L1 expression. Method: NIVO + IPI + 2 cycles of platinum-doublet chemotherapy 790 patients with advanced untreated NSCLC were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles) (n = 361) or chemo (4 cycles) alone (n = 358) (control arm). The only preconditions were ECOG performance status 0-1, and no known sensitizing EGFR/ALK alterations. The patients were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous). Patients were treated with immunotherapy until disease progression, unacceptable toxicity, or for two years. Endpoints The primary endpoint of CheckMate 9LA was overall survival. Statistically, the target hazard ratio was 0.75 and the statistical power was more than 80%. The secondary endpoints, which were tested directly, were progression-free survival response and efficacy related to PD-L1 expression status. Results CheckMate 9LA has shown a significant improvement in overall survival – corresponding to a...