CheckMate 9LA trial

Background

Phase III open-label RCT, N=719, untreated stage IV/recurrent NSCLC, EGFR/ALK wt, any PD-L1 level or histology.

Interventions and follow up

Arm A: Nivolumab 360 mg q3wk + ipilimumab 1 mg/kg q6wk + chemotherapy* q3wk x2 cycles
Arm B: Chemotherapy* alone q3wk x4 cycles (with maintenance pemetrexed for nonsquamous)
Primary endpoint: OS in all patients
mFollow up: 13.2 mo

Results

mOS: 15.6 vs 10.9 mo (A vs B); HR 0.66, 95%CI 0.55-0.80; P=.0006
12-mo OS: 63% vs 47%
mPFS: 6.7 vs 5.0 mo; HR 0.68, 95%CI 0.57-0.82
mOS PD-L1 <1%: 16.8 vs 9.8 mo; HR 0.62, 95%CI 0.45-0.85
mOS PD-L1 ≥1%: 15.8 vs 10.9 mo; HR 0.64, 95%CI 0.50-0.82
mOS PD-L1 1-49%: 15.4 vs 10.4 mo; HR 0.61, 95%CI 0.44-0.84
mOS PD-L1 ≥50%: 18.0 vs 12.6 mo; HR 0.66 (95%CI per report)

Adverse events

Hematologic gr3-4 (A vs B): neutropenia 7% vs 9%; anemia 6% vs 14%
GI gr3-4: diarrhea 4% vs 1%
Immune-related: grade 3-4 treatment-related AEs ~47% vs 38%; ipilimumab-driven irAEs (colitis, hepatitis, endocrinopathy) more frequent in combination arm

Conclusions

Nivolumab + ipilimumab + 2 cycles of chemotherapy significantly improved OS vs chemotherapy alone in first-line advanced NSCLC, regardless of PD-L1 or histology. Chemotherapy*: squamous = carboplatin AUC 6 + paclitaxel; nonsquamous = carboplatin (or cisplatin) + pemetrexed.

Key Limitations

Open-label. No head-to-head vs chemo-pembrolizumab. Dual-IO regimen adds ipilimumab-related immune toxicity and complexity. Limited follow-up at primary analysis.

Clinical Context

FDA approved nivolumab + ipilimumab + 2 cycles platinum chemotherapy first-line for metastatic NSCLC, no EGFR/ALK (May 2020). ESMO lists it among preferred first-line chemo-IO options; the limited 2-cycle chemo backbone is attractive for reducing chemotherapy exposure.

References