Background: HB002.1T is a recombinant human vascular endothelial growth factor receptor (VEGF)-IgG Fc fusion protein, which functions as a decoy receptor to bind VEGF-A, VEGF-B and placental growth factor (PlGF). In phase Ia, HB002.1T monotherapy showed encouraging anti-tumor activity in gallbladder cancer. Methods: This study aimed to evaluate efficacy and safety of HB002.1T plus chemotherapy (mainly based on platinum, paclitaxel, gemcitabine, etc.) in advanced solid tumors. The tumor assessment was evaluated by investigator according to RECIST v1.1. The study included part 1 and part 2, part 1 study was dose escalation (12mg/kg, 16mg/kg Q3W) and dose expansion conducted in patients (pts) with advanced solid tumors, part 2 study was dose expansion (16mg/kgQ3W) in specified tumors (cohort 1: ovarian and cervical, cohort 2: pancreatic, gallbladder and bile duct cancer). Results: As of Dec 20,2022,68 (42F/26M) advanced solid tumor pts were enrolled in the study with 32 pts in part 1 and 36 pts in part 2. 33.3% pts failed at least 3 lines of therapy before enrollment. 63(92.6%) pts had stage IV disease. Median age was 58. It is to be note that 12 efficacy assessment evaluablepts with ovarian cancer (1 with 12mg/kg in part 1,11with 16mg/kg in part 2) were all stage IV, which included 3 complete response (CR),6 partial responses (PR) and 3 stable disease (SD). Median progression free survival (PFS) was 7.3 months and 6-month PFS rate was 58.3%. The ORR and DCR were 75%, 100% respectively. The most common treatment related adverse events (TRAEs) included neutropenia (9/12, 75.0%) and leukocytopenia (8/12, 66.7%). 8 (8/12, 66.7%) pts had grade ≥ 3 TRAEs, which neutropenia (4/12, 33.3%) and leukocytopenia (3/12, 25.0%) were commonly observed. Part 1: In 28 pts whose tumor assessment were available, including 1 gastric cancer patient achieved CR, 11 pts achieved PR (2 gastric, 2 ovarian, 2 cervical, 1 maxillary, 1 lung, 1 parotid, 1 nasopharynx, 1 pancreatic) and 15 achieved SD. Part 2: 32 pts were available for tumor assessment, including 4 achieved CR (3 ovarian, 1 cervical), 10 achieved PR (4 ovarian, 2 cervical, 3 bileduct, 1 pancreatic), and 16 achieved SD. Overall, in Part 1 and 2, TRAEs occurred in 64 (64/68, 94.1%) pts. The most common TRAEs were leukocytopenia (28/68, 41.2%), neutropenia (26/68, 38.2%) and proteinuria (25/68, 36.8%). 34 (34/68, 50.0%) pts had grade ≥ 3 TRAEs, which neutropenia (15/68, 22.1%) and leukocytopenia (11/68, 16.2%) were commonly observed. TRAE leading to discontinuation occurred in 3 pts. No death was reported related with HB002.1T. Conclusions: The Pts were well tolerated to 12mg/kg and 16mg/kg HB002.1T dose combined with chemotherapy, and HB002.1T showed acceptable safety profile. As well as, promising anti-tumor activity was observed in various tumors, especially in advanced ovarian cancer. More data is being accumulated, and confirmatory clinical trials are being prepared. Clinical trial information: NCT04802980.