Between September 2019 and April 2021, 42 pts with a median age of 52 years (IQR:47-58) were enrolled. In the efficacy-evaluable population (n=39), the ORR of 61.5% (24/39, 95% CI:44.9 - 75.9) and the DCR was 94.9% (37/39, 95% CI:80.7 - 98.8). The mPFS was 9.4m (95%CI:8.02-11.63) and the median response time was 1.71m (95%CI:1.38-2.76). Targeted next-generation sequencing was performed using a 520-gene panel (OncoScreen Plus, Burning Rock Biotech) to identify genetic alterations that might be associated with treatment response in 39 pts. Frequently mutated genes included PIK3CA (31%), FAT1 (23%), PRKDC (21%), KMT2D (18%), and TP53 (8%). Our results demonstrated that harboring mutations in PIK3CA alone, other genes related to PI3K-AKT signaling pathway, or KMT2D was associated with significantly better objective response (p<0.05). Conversely, mutations in STK11 was associated with significantly poorer objective response to the combination therapy (p<0.05)...Anlotinib plus sintilimab showed a promising efficacy with a favorable toxicity profile for pts with advanced CC.