JCSE01.11 Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC)

Abstract

Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase II anlotinib-based trial (NCT03628521). Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0. From Septembe-2018 to February-2019, 22 patients were enrolled. All are under treatment and have received at least one tumor assessment as of Apr-8th-2019. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. Among all, 15 achieved PR (7 confirmed, the rest waiting for next assessment), 7 achieved SD, ORR was 68.2% and DCR was 100%. Two grade 3 TRAE occurred with no grade 4/5 observation. The most common TRAE were hematuria, hyperuricemia, hypertension, increased ALT and rash, etc. No unexpected AE observed. Of 21 PD-L1-evaluable patients, 13 (61.9%) were PD-L1+ and showed higher ORR than PD-L1 patients. 16 patients got TMB status (details in table). Notably, 7 of 9 patients achieved SD developed cavities, suggesting a synergetic anti-tumor effect from combination regimen. In this interim analysis, sintilimab plus anlotinib showed high ORR (68.2%) and DCR (100%) with good tolerability, supporting worthy of further development from this convenient usage of chemo-free regimen in first line setting.