This is a multicenter, open-label, phase I/IIa to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of pan-KRAS inhibitor JAB-23E73 in patients with advanced solid tumors harboring KRAS mutations or amplification. The study consists of 2 phases: Phase 1 Dose Escalation and Phase IIa Dose Expansion.
Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer with evidence of KRAS gene alteration (including gene mutation and wild type amplification).
Able to provide an archived tumor tissue sample or fresh biopsy sample.
Life expectancy ≥3 months at the start of treatment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Unable to swallow oral medications or with gastrointestinal dysfunction or gastrointestinal disease that significantly alters the absorption of medication.
Previous treatment with rat sarcoma (RAS) targeting agents.
Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
Impaired cardiovascular function or clinically significant cardiac disease.