Background: Immunotherapy has resulted in significant and lasting clinical responses in non-small lung cancer (NSCLC), esophagus cancer, gastric cancer, colorectal cancer etc. However, most patients (pts) inevitably lose efficacy due to acquired resistance. This study (NCT04169672) aimed to investigate the efficacy and safety of surufatinib (a multi-kinase inhibitor of VEGFR1-3, FGFR1 and CSF1R) plus toripalimab (monoclonal humanized IgG4 programmed death 1 [PD-1] antibody) in pts with advanced solid tumors. Here, we reported the results from pts who bore different tumors and failed in previous treatments containing the checkpoint inhibitors. Methods: Eligible pts were 18~75 years old who had advanced solid tumors and received prior PD-1/programmed death-ligand 1 (PD-L1) antibody therapy for at least 3 months (m) before disease progression. Enrolled pts received surufatinib 250 mg orally once daily and toripalimab 240 mg intravenously every three weeks in a 21-day cycle. The primary endpoint was the objective response rate (ORR) per RECIST v1.1. Secondary endpoints include disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: As of data cutoff (Feb 28, 2023), a total of 28 pts were enrolled and received at least one dose of study treatment. Pts with PD-L1 combined positive score (CPS) ≥1 accounted for 67.9%. 9 pts were diagnosed with gastric cancer /gastroesophageal junction adenocarcinoma (GC/GEJ), 4 pts each with esophageal cancer, NSCLC or intestinal cancer, 2 pts with biliary tract cancer, 1 pt each with other 5 tumors. 39.3% of pts received ≥2 previous anti-tumor therapies. A variety of PD-1 antibodies were used before enrollment, which included tislelizumab (25.0%), sintilimab (17.9%), camrelizumab (14.3%), toripalimab (14.3%), pembrolizumab (7.1%), nivolumab (3.6%), etc. The median exposure duration was 4.1m for study treatment. In 27 tumor evaluable pts, the confirmed ORR and DCR were 7.4 % and 66.7%, respectively. In 28 intent-to-treat pts, the median PFS and OS were 3.94m (95% CI 1.38, 4.21) and 13.04m (95% CI 8.64, 21.59), respectively. The median survival follow-up duration was 20.90m (95% CI 16.10, 25.03). In 9 pts with GC/GEJ, the median PFS and median OS were 2.72m and 13.69m, respectively. Treatment related adverse events (TRAE) occurred in 89.3% of pts. Grade≥3 TRAEs occurred in 39.3% of pts with blood pressure increased (10.7%) and liver injury (7.1%) reported most commonly. 28.6% of pts had immune-related adverse events, among which immune-related pneumonitis (7.1%) and immune-related diabetes (7.1%) reached G3. Two TRAEs led to surufatinib discontinuation. No deaths related to either surufatinib or toripalimab. Conclusions: Surufatinib plus toripalimab showed antitumor activity and a manageable safety profile in pts with advanced solid tumors progressing after immunotherapy, especially in GC/GEJ.