497P - Sintilimab in combination with anlotinib in advanced NSCLC treated with first-line PD-1 antibodies: An open, single-arm, phase II trial

Background

Immune checkpoint inhibitors (ICIs) has been shown to be effective and has become the standard of care as first-line treatment of advanced NSCLC. Multiple previous studies of tumors have allowed the continued use of anti-PD-1 antibody therapy after first-line treatment progress. Subgroup analyses of these studies showed that 13-33% of patients receiving anti-PD-1 antibody therapy after progress achieved partial response (PR). The combination of ICIs and anti-angiogenic therapy has a synergistic anti-tumor effect and can improve the prognosis of patients. This study was designed to evaluate the efficacy and safety of sintilimab in combination with anlotinib in NSCLC disease progressed after first-line treatment with anti-PD-1 antibody.

Methods

An open, single-arm, phase II trial was designed, which enrolls NSCLC patients with disease progression after first-line treatment with anti-PD-1 antibody. Sintilimab (200 mg, day 1) in combination with anlotinib (12mg, day 1 to 14) were given every 3 weeks. Primary end point is objective response rate (ORR) evaluated via RECIST 1.1. Key secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety (CTCAE 5.0).

Results

From 3/2021 to 6/2023, 17 patients were enrolled. The median age was 63 years old (range 45-73) and 100% (17/17) was male. In 14 patients with efficacy data, 14.3% (2/14) achieved partial response (PR) and 71.4% (10/14) achieved stable disease (SD). ORR and DCR were 14.3% (and 85.7%, respectively. Until the last follow-up, the median PFS was 6.0 months（95% CI, range 4.2-7.7 months）, 6-month PFS rate was 56.4%. The median OS was 17.9 months（95% CI, range 5.6-NA months）, 12-month OS rate was 64.6%. Grade 3/4 treatment-related adverse events (TRAEs) included: hand and foot skin reaction (5.9%, 1/17), increased alanine aminotransferase (5.9%, 1/17), hypertension (11.8%, 2/17), hypertriglyceridemia (5.9%, 1/17) and neutropenia (5.9%, 1/17). No treatment-related deaths occurred.

Conclusions

Given the encouraging anti-tumor activity and favorable tolerability, the combination of sintilimab and anlotinib could be an effective and safe option for NSCLC.

Clinical trial identification

Clinical trial information: NCT04691388.

Editorial acknowledgement

Legal entity responsible for the study

Xinmin Yu.

Funding

1. Innovent Biologics, Inc. 2. Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.