Glecirasib, an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12 (KRAS G12C), has exhibited clinical activity in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Here, we investigated the efficacy and safety of glecirasib in patients with pancreatic ductal adenocarcinoma (PDAC) and other solid tumors (excluding NSCLC and CRC) that rarely harbor the KRAS G12C mutation but for which effective treatment options remain limited.We conducted and analyzed two open-label, phase I/II trials in adult patients with KRAS G12C mutant solid tumors, in which glecirasib was administered orally. The two trials had similar eligibility criteria and endpoints but differed in the regions of patient recruitment. We performed a pooled analysis of all patients, excluding NSCLC and CRC, from both trials. The primary endpoint in the pooled population was objective response rate (ORR). Efficacy and safety were assessed in patients who received at least one dose of glecirasib.As of June 30, 2024, the pooled analysis included 54 patients who were treated with glecirasib: 32 PDACs, 8 biliary tract cancers (BTCs), 4 small intestinal cancers, 3 gastric cancers, 2 appendiceal cancers, and 5 other tumors. At baseline, 24 received ≥ two prior lines of systemic therapy. Of the 53 efficacy-evaluable patients, the confirmed ORR was 50.9% (95% confidence interval [CI], 36.8%-64.9%), with an ORR of 46.9% (95% CI, 29.1%-65.3%) in PDAC patients. Among other solid tumors, ORR was 71.4% (5/7) in BTC, 100% (4/4) in small intestinal cancer, and 66.7% (2/3) in gastric cancer. Median progression-free survival and median overall survival were 6.9 and 10.8 months, respectively, in the overall population, and 5.5 and 10.8 months, respectively, in patients with PDAC. Treatment-related adverse events (TRAEs) of any grade occurred in 94.4% patients, with grade ≥ 3 TRAEs in 27.8%. No fatal TRAEs or TRAEs leading to treatment discontinuation occurred.Glecirasib showed promising efficacy and was well tolerated in patients with PDAC and other advanced solid tumors (beyond NSCLC and CRC), warranting further expedited clinical development in this patient population.ClinicalTrials.gov identifier: NCT05009329 and NCT05002270.© 2025 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.