Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC

BackgroundDespite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC).MethodsThis multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-na & iuml;ve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part.ResultsThe MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m2)/cisplatin (75 mg/m2) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m2)/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m2)/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2-7.5 months), overall survival (29.7 months vs. 16.1-21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months).ConclusionsThe combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin.Trial registrationThe trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017.A significant unmet medical need still exists in patients with PD-L1-unselected NSCLC due to the limited efficacy of immune checkpoint inhibitors and the lack of a well-defined, effective treatment approach.Spartalizumab in combination with platinum doublet chemotherapy (PDC), with/without canakinumab, was well tolerated across treatment groups.Spartalizumab plus PDC, with/without canakinumab, showed the antitumor activity in this clinical setting.Addition of canakinumab did not appear to improve the antitumor activity of the combination of spartalizumab with pemetrexed plus cisplatin.