LBA57 - Sintilimab plus anlotinib versus platinum-based chemotherapy as first-line therapy in metastatic NSCLC (SUNRISE): An open label, multi-center, randomized, phase II study

Background

“Chemo-free” strategy of anti-PD-1 antibody sintilimab combining angiogenesis modulator anlotinib had shown potential clinical benefit in our phase I study in treatment naïve advanced NSCLC. Here we presented the first phase Ⅱ randomized trial comparing sintilimab plus anlotinib with chemo in treatment-naïve metastatic NSCLC.

Methods

This open label, phase II study were conducted at 6 sites. Previously untreated, stage IV, EGFR/ALK/ROS1 negative NSCLC pts were eligible. Pts were randomly assigned (1:1) to Arm A (sintilimab 200mg Day 1, anlotinib 12 mg, QD 1-14) or Arm B (platinum-based chemotherapy, cross-over to sintilimab were allowed after disease progression [PD]), stratified by histology and PD-L1 expression. Treatment was given every 3 weeks until PD, intolerable toxicity, withdrawal, or death. Sintilimab was given up to 24 months or 35 cycles. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS) and safety.

Results

Between Nov. 2019 to Jul. 2022, 89 pts were randomized (43 to Arm A, 46 to Arm B). As of Jul. 15th 2022, median follow-up was 13.1 months and 84 pts were evaluable (41 vs 43). ORR was 50.0% (95% CI [33.8-66.2]) in Arm A compared with 32.6% (95% CI [19.1-48.5] in Arm B, with a DoR of 16.3 vs 6.2 mo. DCR was 85.0% (95% CI [70.2-94.3]) vs 93.0% (95% CI [80.9-98.5]), and the median PFS was 10.8 vs 5.7 mo (HR 0.4; 95% CI[0.25-0.74]). OS was not matured. Grade 3-4 treatment-related adverse events(TRAE) occurred in 11.6 % vs 43.5% pts in arm A and B, respectively. Hypothyroidism, hyponatremia and AST increased were most frequently observed in Arm A. 2 pts experienced treatment discontinuation and 1 died due to TRAE in Arm B, while none were observed in Arm A.

Conclusions

In this preliminary interim analysis, sintilimab plus anlotinib suggested a trend towards improving response and survival compared with chemotherapy in treatment naïve metastatic NSCLC. Statistical hypothesis testing will be conducted with at least 87 evaluable patients as pre-planned.

Clinical trial identification

NCT04124731.

Editorial acknowledgement

Legal entity responsible for the study

Baohui, Han.

Funding

Innovent Biologics, Chia Tai Tianqing Pharmaceutical.

Disclosure

All authors have declared no conflicts of interest.