CheckMate-9LA: Nivolumab + Ipilimumab in Advanced NSCLC – Two-Year Update

In the randomized phase 3 CheckMate-9LA trial, patients with advanced non–small-cell lung cancer (NSCLC) who were treated with first-line nivolumab (NIVO) plus ipilimumab (IPI) in addition to 2 cycles of chemotherapy experienced significantly improved overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) compared with chemotherapy alone (4 cycles). Clinical benefit was observed regardless of PD-L1 expression level and histology status. The researchers reported efficacy data with ≥2 years of follow-up at ASCO 2021.¹

Adult patients with stage IV recurrent NSCLC, Eastern Cooperative Oncology Group performance status of 0 or 1, and no known sensitizing EGFR or ALK alterations were stratified by PD-L1 score (<1% vs ≥1%), sex, and histology (squamous vs nonsquamous). Patients were randomized 1:1 to NIVO 360 mg every 3 weeks plus IPI 1 mg/kg every 6 weeks + 2 cycles of chemotherapy (n = 361) or 4 cycles of chemotherapy (n = 358). Patients with nonsquamous NSCLC in the chemotherapy-alone arm could receive pemetrexed maintenance. The primary end point was OS, secondary end points included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels with safety as an exploratory end point.¹

After a follow-up of ≥24.4 months, patients treated with NIVO/IPI + chemotherapy derived an increase in OS compared with chemotherapy alone.¹ The median OS for NIVO/IPI + chemotherapy was 15.8 months versus 11.0 months for chemotherapy alone (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.61-0.86), and 2-year OS rates were 38% versus 26%, respectively.¹ NIVO/IPI + chemotherapy resulted in a median PFS of 6.7 months versus 5.3 months for chemotherapy alone (HR, 0.67; 95% CI, 0.56-0.79) with 8% and 37% of patients who had disease progression receiving subsequent immunotherapy, respectively.¹ ORR was 38% with NIVO/IPI + chemotherapy with a median DOR of 13.0 months compared with 25% ORR with chemotherapy and a median DOR of 5.6 months with similar clinical benefit observed in all randomized patients and across the majority of subgroups, including by PD-L1 expression level and histology.¹

All grade and grade 3/4 treatment-related adverse events were reported in 92% and 48% of patients in the NIVO + IPI + chemotherapy arm, compared with 88% and 38% in the chemotherapy-alone arm.¹

With 2 years of minimum follow-up, first-line NIVO/IPI + chemotherapy demonstrated durable survival and other efficacy benefits relative to chemotherapy in patients with advanced NSCLC, and no new safety signals were identified.¹

Reference

1. Reck M, Ciuleanu T-E, Cobo M, et al. First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): two-year update from CheckMate 9LA. American Society of Clinical Oncology (ASCO), June 2021; Abstract 9000.