The goal of this trial is to learn if KQB548 works to treat patients with advanced solid malignancies with a KRAS G12D mutation. It will also learn about the safety of KQB548. The main questions it aims to answer are:

• What is the safe dose of KQB548?
• Does KQB548 decrease the size of the tumor?
• What happens to KQB548 in the body?

Inclusion Criteria:

• Pathologically confirmed, locally advanced or metastatic PDAC, CRC, or NSCLC with a KRAS G12D mutation
• Progressed on, or intolerant to at least one prior line of systemic standard of care therapy
• Measurable disease according to RECIST v1.1
• Adequate organ function

Exclusion Criteria:

• Previous treatment with a KRAS G12D inhibitor or pan-RAS inhibitor
• History of intestinal disease, uncontrolled inflammatory bowel disease (e.g., Crohn's disease, Ulcerative Colitis), major esophageal or gastric surgery, or other gastrointestinal conditions (e.g., uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study intervention or result in inability to swallow oral medications
• Poorly controlled ascites and/or pleural effusion
• Requires treatment with a strong and/or moderate CYP3A inhibitor or inducer
• Requires treatment with a proton-pump inhibitor