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.

Study JAB-23E73-1001 is a global multicenter, open-label Phase 1/2a study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anticancer activity of JAB-23E73 as a single agent in adult patients with advanced solid tumors with KRAS alteration. This study consists of a Phase 1a dose-escalation, followed by Phase 1b dose-expansion (dose optimization) and Phase 2a indication expansion. After completing dose-escalation, the MTD or preliminary RP2D of JAB-23E73 will be determined. Then, two of the alternative dosages of JAB-23E73 will be selected to further evaluate the efficacy, safety and PK in patients with KRAS-alternated NSCLC or other tumors, and patients may be further selected by certain/several types of KRAS-alternations based on dose escalation data. The RP2D will be determined according to the safety, efficacy and PK data from phase 1b.

Inclusion Criteria:

1. 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).
2. Able to provide an archived tumor tissue sample or fresh biopsy sample.
3. Life expectancy ≥3 months at the start of treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. ≥1 measurable lesion per RECIST v1.1.
6. Adequate organ function.

Exclusion Criteria:

1. Unable to swallow oral medications or with gastrointestinal dysfunction or gastrointestinal disease that significantly alters the absorption of medication.
2. Previous treatment with rat sarcoma (RAS) targeting agents.
3. Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
4. Impaired cardiovascular function or clinically significant cardiac disease.
5. Mean QT interval corrected using Fridericia's formula (QTcF) >470 msec.
6. Females who are pregnant or breastfeeding.