Nivolumab ( Opdivo ) + Ipilimumab ( Yervoy ) was shown to improve overall survival ( OS ) and durability of response versus chemotherapy in first line ( 1L ) advanced non-small cell lung cancer ( NSCLC ) in CheckMate 227 Part 1, regardless of PD-L1 expression.
Researchers have hypothesized that a limited course of chemotherapy combined with Nivolumab + Ipilimumab could provide rapid disease control while building on the durable overall survival benefit seen with dual PD-1 and CTLA-4 inhibition.
CheckMate 9LA is a phase 3 randomized study evaluating Nivolumab + Ipilimumab + 2 cycles chemotherapy versus chemotherapy in first line stage IV / recurrent NSCLC.
Adults with treatment-naive, histologically confirmed stage IV / recurrent NSCLC, ECOG performance status 0–1, and no known sensitizing EGFR / ALK alterations were randomized 1:1 to Nivolumab 360 mg Q3W ( every three weeks ) + Ipilimumab 1 mg/kg Q6W ( every six weeks ) + chemotherapy ( 2 cycles ) ( n = 361 ) or chemotherapy ( 4 cycles ) alone ( n = 358 ), stratified by PD-L1 ( less than 1% vs 1% or more ), sex, and histology ( squamous vs non-squamous ).
Chemotherapy was based on histology. Patients with non-squamous NSCLC in the chemotherapy-only arm could receive optional Pemetrexed maintenance.
Patients were treated with immunotherapy until disease progression, unacceptable toxicity, or for 2 years.
The primary endpoint was overall survival; the interim analysis using Lan–DeMets alpha spending function with O’Brien–Fleming boundary was planned at ~80% information fraction ( ie, after observing ~322 total events ).
Secondary endpoints included progression-free survival ( PFS ) and objective response rate ( ORR ) by blinded independent central review, and efficacy by PD-L1 subgroups.
Exploratory endpoints included safety / tolerability.
Baseline characteristics were balanced across arms.
At a preplanned interim analysis ( minimum follow-up 8.1 months ), overall survival was significantly prolonged with Nivolumab + Ipilimumab + chemotherapy versus chemotherapy ( hazard ratio, HR=0.69, 96.71% CI: 0.55–0.87; P = 0.0006 ); statistically significant improvements in progression-free survival and objective response rate were seen.
With longer follow-up ( minimum 12.7 months ), Nivolumab + Ipilimumab + chemotherapy versus chemotherapy continued to provide longer overall survival; median 15.6 vs 10.9 months ( HR=0.66, 95% CI: 0.55–0.80 ); 1-year OS rates were 63% vs 47%.
Clinical benefit was consistent across all efficacy measures in key subgroups including by PD-L1 and histology.
Grade 3–4 treatment-related adverse events were reported in 47% vs 38% of patients in the Nivolumab + Ipilimumab + chemotherapy versus chemotherapy arms, respectively.
In conclusion, CheckMate 9LA met its primary endpoint; a statistically significant improvement in overall survival was observed with Nivolumab + NSCLC-optimized Ipilimumab + a limited course of chemotherapy vs chemotherapy ( 4 cycles ) in first line advanced NSCLC.
No new safety signals were reported. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020