HSK41959 With Standard Therapy in Solid Tumors With MTAP Deletion

Inclusion criteria

• Adult participants aged 18 years or older.
• ECOG performance status of 0 to 1.
• Life expectancy of at least 3 months.
• Histologically or cytologically confirmed advanced malignant tumor with MTAP deficiency identified by a validated assay.
• At least one measurable lesion according to RECIST version 1.1.
• For NSCLC cohorts: advanced or metastatic NSCLC meeting protocol-specified disease characteristics and prior treatment requirements.
• For PDAC cohorts: advanced or metastatic PDAC meeting protocol-specified disease characteristics and prior treatment requirements.
• Adequate bone marrow, hepatic, renal, and coagulation function.
• Willingness to provide tumor tissue and/or undergo protocol-required biomarker testing, if applicable.

Exclusion criteria

• Prior exposure to agents targeting the MAT2A or PRMT5 pathway.
• Prior antitumor therapy or unresolved toxicities not meeting protocol-defined washout/recovery requirements.
• Known actionable driver alterations or prior therapies excluded by the protocol for specific NSCLC cohorts (for example EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, KRAS G12C, HER2, as applicable).
• Significant gastrointestinal disorders that may affect drug absorption.
• Clinically significant cardiovascular disease, including clinically relevant QTc prolongation, reduced left ventricular ejection fraction, or severe heart failure.
• Uncontrolled metabolic disease, uncontrolled hypertension, or active infection.
• Known HIV infection, active hepatitis B with significant viral replication, or active hepatitis C infection.
• Use of prohibited concomitant medications, including strong inhibitors or inducers of CYP3A4, P-gp, BCRP, or other protocol-specified transporters/enzymes within the required washout period.
• Other serious medical or psychiatric conditions that, in the investigator's judgment, would make study participation inappropriate.