Background: Given the synergy effect of immunotherapy and antiangiogenic 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 (multitarget TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is also one arm from phase I anlotinib-based trial (NCT03628521). Method: 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. Result: From Septembe-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/ current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least one tumor assessment as of Jul-3 th -2019. Among all, 17 achieved confirmed PR, 5 achieved SD, ORR was 77.3% and DCR was 100%. 6m-PFS rate was 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 7 (31.8%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE were hematuria, hyperuricemia, hypertension, increased ALT and rash, etc. 21 patients had baseline PD-L1-evaluated and 17 patients got TMB status (details in table). Notably, 2 of 5 SD patients developed cavities inside, suggesting a sign of synergetic anti-tumor effect from combination regimen. Conclusion: In this interim analysis, sintilimab plus anlotinib showed high ORR (77.3%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.

No abstract