A Pilot Study of Nintedanib in Molecularly Selected Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (NCT02299141).

e21694 Background: Nintedanib is a small molecule tyrosine kinase inhibitor targeting VEGFR1-3, PDGFR and FGFR. The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in TP53, VEGFR1-3, PDGFR-A, PDGFR-B, and FGFR1-3 treated with nintedanib as part of an open label, single arm pilot study. Methods: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with ECOG PS≤1 and adequate organ function were enrolled. Exclusion criteria included cavitary or necrotic tumors with invasion of major blood vessels, history of recent thromboembolic events, predisposition to bleeding or thrombosis, myocardial infarction and weight loss > 10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily during each 28-day cycle until disease progression or unacceptable toxicity. Response assessments were performed every 8 weeks. The primary endpoint was overall response (ORR) by RECIST 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. Results: Between 5/7/2015 and 11/15/2019, 20 patients were enrolled to study. The median age was 66 years, 15/20 (75% were females), 17/20 (85%) had received prior immunotherapy and 11/20 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with 3/20 partial responses (PR), while 12 patients had stable disease (SD), with disease control (PR+SD≥16 weeks) rate of 60% (12/20). The median progression-free survival and median overall survival were 18 weeks (95% CI: 8-31) and 48 weeks (95% CI:15-56) respectively. All three responders had a TP53 mutation and had received prior immunotherapy. There were nine grade 3 events including transaminitis in 20%, while one patient each (5%) experienced hyperbilirubinemia, anorexia, fatigue, hypertension, and nausea. Grade 4 events included transaminitis (10%) and cerebral edema (5%). There was one grade 5 cardiac event, which was unrelated to nintedanib. Conclusions: In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity. Clinical trial information: NCT02299141.