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.
Sequential
JAB-23E73
DrugAdministered orally
JAB-23E73
DrugAdministered orally
Phase 1: Number of participants with dose limiting toxicities (DLT)
Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. DLTs will be defined as the occurrence of any of the toxicities as described in the protocol.
Phase 2a: Objective response rate (ORR)
ORR is defined as the proportion of patients with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1.
Phase 1/2a: Adverse events
Incidence and severity of treatment-emergent Adverse Events (TEAEs), treatment-related Adverse Events (TRAEs) and serious Adverse Events (SAEs)
Phase 1/2a: Pharmacokinetic (PK): Maximum concentration (Cmax) of JAB-23E73
PK: Cmax of JAB-23E73
Phase 1/2a: PK: Time to Maximum Concentration (Tmax) of JAB-23E73
PK: Tmax of JAB-23E73
Phase 1/2a: PK: Area Under the Concentration Versus Time Curve (AUC) of JAB-23E73
PK: AUC of JAB-23E73
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