This study is to evaluate the safety and tolerability of pan-KRAS inhibitor JAB-23E73 in adult participants with advanced solid tumors
Written informed consent.
Participant must be ≥18 years of age at the time of signing the Informed Consent Form (ICF).
Histologically or cytologically confirmed locally advanced or metastatic solid tumors that are not suitable for curative interventions.
Patients must have KRAS alterations.
Inability to swallow oral medications, or presence of gastrointestinal dysfunction or gastrointestinal disorders that may significantly alter the absorption of the study drug.
Patients who have previously been treated with KRAS G12C inhibitors, KRAS G12D inhibitors, or pan/multi-KRAS inhibitors.
Known serious allergy to JAB-23E73 or excipient.
Patients with primary central nervous system tumors.
Sequential
JAB-23E73
DrugOral administration
JAB-23E73
DrugOral administration
JAB-23E73
DrugOral administration
Dose Escalation (Phase 1a): Determine the Maximum tolerated dose (MTD) of JAB-23E73 monotherapy.
Number and proportion of patients who experience at least 1 dose-limiting toxicity (DLT) during the first 21 days of treatment. A DLT is defined as any toxicities that meet the criteria for a DLT assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 during the evaluation period at any dose.
Dose Escalation (Phase 1a): Evaluate the overall safety and tolerability of JAB-23E73.
Safety and tolerability of repeated cycles from first drug administration up to the Safety Follow Up Visit (SFUV)
Dose Expansion/Optimization (Phase 1b): Determine the Recommended Phase 2 Dose (RP2D) of JAB-23E73 in patients with KRAS- alternated NSCLC or other selected tumors.
RP2D determined by MTD, long term tolerability, PK, efficacy and any other relevant data as available.
Indication Expansion (Phase 2a): Evaluate the preliminary antitumor activity of JAB-23E73 monotherapy at the RP2D in patients with advanced or metastatic CRC, PDAC, and other solid tumors.
ORR, defined as the percentage of patients with the best overall response of confirmed partial response (PR), or complete response (CR) per RECIST v1.1.
Dose Escalation (Phase 1a): Overall Response Rate (ORR)
Objective response rate (ORR) defined as the percentage of patients with the best overall response of confirmed partial response (PR), or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Dose Escalation (Phase 1a): Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Cmax of JAB-23E73
Dose Expansion/Optimization (Phase 1b): Overall Response Rate (ORR)
ORR, defined as the percentage of patients with the best overall response of confirmed PR, or CR per RECIST v1.1.
Dose Expansion/Optimization (Phase 1b): Evaluate the overall safety and tolerability of JAB-23E73.
Safety assessments including but not limited to TEAEs, SAEs, deaths and changes in clinical laboratory measures.
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