Adding ipilimumab to nivolumab did not improve survival in patients with advanced, previously treated, immunotherapy-naive squamous non-small cell lung cancer (NSCLC), according to phase 3 trial results published in JAMA Oncology.1

In previous phase 3 studies, nivolumab plus ipilimumab, given with and without chemotherapy, improved survival when compared with chemotherapy alone in the first-line setting for patients with advanced NSCLC.2,3

Researchers conducted the phase 3 Lung-MAP S1400I trial ( Identifier: NCT02785952) to determine if adding ipilimumab to nivolumab can improve outcomes in patients with advanced, previously treated, immunotherapy-naive squamous NSCLC.

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The trial included 252 eligible patients who had a mean age of 67.5 years (range, 41.8-90.3 years). A majority of patients were men (67%), and most were White (82%).

Two-thirds of patients (66%) had received at least 1 prior systemic therapy for stage IV or recurrent disease, 34% had received localized radiation, and 34% had received radiation with curative intent. 

The patients were randomly assigned 1:1 to receive nivolumab plus ipilimumab (n=125) or nivolumab alone (n=127) until their disease progressed or they experienced intolerable toxic effects.

The trial was terminated for futility at a planned interim analysis. The median follow-up in surviving patients was 29.5 months.

Overall survival (OS), the primary endpoint, was similar between the treatment arms (hazard ratio [HR], 0.87; 95% CI, 0.66-1.16; P =.34). The median OS was 10 months for the nivolumab-ipilimumab arm and 11 months for the nivolumab-alone arm.

Likewise, there was no significant difference in investigator-assessed progression-free survival (PFS) between the 2 arms (HR, 0.80; 95% CI, 0.61-1.03; P =.09). The median PFS was 3.8 months with nivolumab-ipilimumab and 2.9 months with nivolumab alone. 

The median duration of response was 28.4 months in the combination arm and 9.7 months in the monotherapy arm. The objective response rate was 18% and 17%, respectively.

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 39.5% of patients who received the combination and 33.3% of those who received nivolumab alone. Fatigue and pneumonitis were the most common grade 3 or higher TRAEs in both groups.

Treatment was discontinued due to toxic side effects in 25% of patients in the combination arm and 15% of those in the monotherapy arm. There were 3 treatment-related deaths in the combination arm and 1 death in the monotherapy arm.

Disclosures: This research was supported by grants from the Foundation for the National Institutes of Health to the Southwest Oncology Group. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Gettinger SN, Redman MW, Bazhenova L, et al. Nivolumab plus ipilimumab vs nivolumab for previously treated patients with stage IV squamous cell lung cancer: The Lung-MAP S1400I phase 3 randomized clinical trial. JAMA Oncol. Published online July 15, 2021. doi:10.1001/jamaoncol.2021.2209
  2. Paz-Ares L, Ciuleanu T-E, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): An international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):198-211. doi:10.1016/S1470-2045(20)30641-0
  3. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381(21):2020-2031. doi:10.1056/NEJMoa1910231.