CheckMate 817: Safety of flat-dose nivolumab (nivo) plus weight-based ipilimumab (ipi) for the first lie (1 L) treatment of advanced non-small cell lung cancer (NSCLC)

Background CheckMate (CM) 227 demonstrated significant, clinically meaningful progression-free survival benefit with 1 L nivo 3 mg/kg Q2W plus low-dose ipi 1 mg/kg Q6W vs. chemotherapy in patients (pts) with advanced NSCLC and tumor mutational burden (TMB) ≥ 10 mutations/Mb. Dose and schedule for this combination were optimized for 1 L NSCLC in CM 012 and further validated in CM 568 and CM 227. Flat dosing of nivo (240 mg Q2W) may simplify treatment while providing comparable exposure, and was recently approved for previously treated NSCLC. CM 817 (NCT02869789) is a multi-cohort, open-label phase 3b/4 study of the safety and efficacy of flat-dose nivo plus weight-based low-dose ipi in recurrent/metastatic NSCLC. We report safety results of this regimen in the 1 L setting from cohort A

Methods Pts with ECOG PS ≤ 1 and previously untreated NSCLC were eligible regardless of tumor programmed death ligand 1 (PD-L1) expression and TMB. Pts received nivo 240 mg Q2W plus ipi 1 mg/kg Q6W for 2 years or until disease progression/unacceptable toxicity. The primary endpoint was safety based on grade ≥ 3 select treatment-related adverse events (TRAEs; defined as AEs of potential immunologic causes).

Results Pts enrolled from October 2016 to August 2017; 391 were treated at 68 academic and community-based centers in Europe and North America. Median age was 65 years and 27.9% of pts had squamous histology. PD-L1 expression was evaluable in 91% of pts; of those, 50% had ≥ 1% tumor PD-L1 expression. At database lock (March 1, 2018), minimum follow-up was 5.4 months and 34.5% of pts remained on treatment. The median (range) number of nivo and ipi doses was 9 (1 – 28) and 3 (1 – 10), respectively. Any grade and grade 3 – 4 TRAEs occurred in 74.4% and 27.6% of pts, respectively; 14.1% discontinued treatment due to TRAEs. Rates of any grade select TRAEs by category ranged from 1.3% (renal) to 28.4% (skin). The most common grade 3 – 4 select TRAEs were hepatic (4.6%), pulmonary (3.1%), and gastrointestinal (3.1%). Of 2 treatment-related deaths, 1 was due to Guillain-Barré syndrome and 1 to rhabdomyolysis leading to heart failure.

Conclusions The safety profile of flat-dose nivo plus low-dose ipi was consistent with previous reports of weight-based nivo plus low-dose ipi optimized for NSCLC. Toxicities were manageable, with no new safety signals identified.