For part 1 of the trial, patients were randomized 1:1:1 to nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks; histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles; and nivolumab 240 mg every 2 weeks or nivolumab 360 mg plus histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles, followed by nivolumab monotherapy.
Of all randomized patients in part 1 (n=1,739), 1,004 (58%) were evaluable for TMB analyses. Of all TMB-evaluable patients, 444 (44%) had TMB greater than or equal to 10 mut/Mb, including 139 patients randomized to nivolumab plus ipilimumab and 160 patients randomized to chemotherapy. TMB was assessed using the validated assay, FoundationOne CDx.
One-year PFS was higher with nivolumab plus ipilimumab than with chemotherapy among all randomized patients in part 1 (30.9% vs. 17.0%; HR for disease progression or death, 0.83; 95% CI, 0.72-0.96).
The PFS was significantly prolonged with the combination, compared with chemotherapy among patients with a high TMB; the 1-year PFS rate was 42.6% versus 13.2%, respectively, and the median PFS was 7.2 months (95% CI, 5.5-13.2) versus 5.5 months (95% CI, 4.4-5.8) respectively (HR for disease progression or death, 0.58; 97.5% CI, 0.41-0.81; P less than .001). In a subgroup analysis, PFS was longer with nivolumab plus ipilimumab versus chemotherapy for patients with a programmed death ligand 1 expression level of at least 1% and those with a level of less than 1%, reported Dr. Hellmann of Memorial Sloan Kettering Cancer Center, New York.