PDR001 in patients with unresectable non-small cell lung cancer (NSCLC) harboring KRAS/NRAS mutation or without actionable genetic abnormalities: Phase II, multicenter, single arm study

Background: PDR001 (spartalizumab) is a humanized PD-1-blocking antibody with reduced Fc-mediated cytotoxicity. It has shown antitumor activity and manageable safety across multiple tumor types, Herein, we present the results of PDR001 for patients with non-small cell lung cancer (NSCLC) without actionable driver mutations Methods: This was a multi-center, open-label, single-arm phase II study. A total of 70 patients with unresectable NSCLC without actionable driver mutations were enrolled between October 5, 2018 and December 17, 2020. Patients were treated with PDR001 (Spartalizumab) 300 mg every 3 weeks until disease progression or intolerable toxicity. Results: At a median follow up of 72.0 months (95% confidence interval [CI], 72 - not evaluable), median overall survival was 14.0 months (95% CI, 10.5 - 24.1), and the median PFS of total patients was 2.8 months (95% CI, 1.8 - 5.9). The disease control rate, and overall response rate was 61.4%, 24.3%, respectively. A total of 43 patients were available for PD-L1 TPS analysis (IHC by 22C3), and patients who showed PD-L1 TPS ≥ 50%, the median OS was 16.1 months (95% CI, 8.9-46.2), which showed trend toward better outcomes compared to patients with PD-L1 TPS < 50%. and median PFS with patients with TPS ≥ 50% showed significantly better outcomes compared to TPS <50% (4.9 months vs. 2.8 months, P = 0.038). A total of 41 patients (58.6%) experienced treatment-related adverse events, the majority of which were grade 1-2 in severity. Grade 3 toxicities occurred in five patients, including rash (n=1), increased alanine aminotransferase (n=1), pneumonitis (n=1), and hyperglycemia (n=2). Two patients discontinued treatment due to adverse events: one because of grade 3 rash and another because of grade 3 pneumonitis. The majority of these AEs resolved upon discontinuation and subsequent steroid treatment. Conclusions: PDR001 exhibited promising clinical efficacy in patients with unresectable NSCLC without actionable driver mutations, exhibited tolerable safety. Future randomized clinical trials are warranted to validate our findings.