Background: KRAS G12C mutation is an oncogenic driver and a validated therapeutic target in solid tumors. Glecirasib, a highly selective, covalent oral KRAS G12C inhibitor, has demonstrated promising clinical activity in NSCLC and CRC; however, the efficacy and safety of glecirasib are unknown in PDAC and other solid tumors with KRAS G12C mutation. Methods: Two phase 1/2 trials (NCT05009329 in China; NCT05002270 in US, Europe and Israel) are evaluating the safety and efficacy of glecirasib in patients (pts) with solid tumor harboring KRAS G12C mutations. As both trials have similar inclusion and exclusion criteria, we have pooled the data from them to assess the effect of glecirasib monotherapy in various types of solid tumor with low incidence of KRAS G12C mutation. Here we report the preliminary efficacy and safety results of glecirasib in pts with PDAC and other solid tumors (excluding NSCLC and CRC) from the pooled population of both trials. Results: As of Sep 8, 2023, a total of 48 pts have received glecirasib monotherapy (41 from NCT05009329 and 7 from NCT05002270) and 47 were evaluable for efficacy. This includes 28 PDAC and 19 other solid tumors (7 biliary tract, 3 gastric, 3 small bowel, 1 appendiceal, 1 hepatocellular, 1 peritoneal, 1 posterior bronchial mediastinal, 1 ameloblastic carcinoma and 1 cervical). At baseline, pts had previously received a median of one line of systemic therapy (range: 0 to 4; with 23 pts have received one prior line); 85% Asian, 15% Caucasian; most (45 pts) at 800 mg QD. Among 28 pts with PDAC, 13 achieved confirmed partial response (PR) with the confirmed objective response rate (ORR) of 46.4% (13/28) and disease control rate (DCR) of 96.4%; the median duration of response (DOR) and progression-free survival (PFS) were 4.1 months and 5.5 months (95%CI 1.2, 13.1), respectively. Among 19 pts with other tumor types, the confirmed ORR of 52.6% (10/19) and DCR of 84.2% (16/19) were observed; the median DOR and PFS were 8.3 months and 7.0 months (95% CI 1.1 to 15.2), respectively. Treatment-related AE (TRAE) of any grade occurred in 89.6% (43/48) pts; the most common (≥10%) TRAE were anemia (52.1%), blood bilirubin increased (39.6%), white blood cell count decreased (18.8%), AST increased (18.8%), diarrhea (16.7%), ALT increased (14.6%), asthenia (14.6%), hypertriglyceridemia (10.4%), and nausea (10.4%); ≥Grade 3 TRAE occurred in 25% (12/48) pts; no TRAE were fatal or led to treatment discontinuation. Conclusions: Glecirasib monotherapy is well tolerated and has a manageable safety profile and exhibits promising anti-tumor activity in pts with KRAS G12C mutated PDAC and other solid tumors. Further clinical development of glecirasib in above mentioned population is ongoing (NCT06008288). Clinical trial information: NCT05009329 and NCT05002270.