Overview
The purpose of this study is to determine the safety and efficacy of pan KRAS inhibitor JAB-23E73 in combination with nab-paclitaxel and gemcitabine in participants with metastatic PDAC harboring KRAS gene alterations.
Description
This is a phase Ib/III, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antineoplastic activity of pan-KRAS inhibitor JAB-23E73 in combination with nab-paclitaxel and gemcitabine in treatment-naive participants with metastatic PDAC.
Phase Ib study：an open-label study, including dose escalation and backfill cohorts, with approximately 40-80 participants planned to be enrolled (including approximately 20-50 participants in the backfill cohort),Aiming to determine the recommended phase III dose \[RP3D\] within investigated patient population groups.
Phase III: Following confirmation of the efficacy and safety of JAB-23E73 in combination with the AG regimen in Phase Ib, a Phase III trial will be initiated to evaluate the efficacy and safety of JAB-23E73 plus AG versus AG alone for the treatment of metastatic PDAC.
Eligibility
Inclusion Criteria:
1.Written informed consent signed by the participant or the participant's legally authorized representative must be obtained prior to performing any study-related procedures. 2. Histologically or cytologically confirmed metastatic PDAC.
3\. No prior systemic antitumor therapy for advanced disease (treatment-naïve). 4. Presence of KRAS gene alterations: be enrolled upon approval by the sponsor).
5\. ECOG performance status score of 0 or 1. 6. Adequate organ function.
Exclusion Criteria:
- Inability to swallow oral medications or the presence of gastrointestinal dysfunction or disease that may significantly alter drug absorption.
- A history of another malignancy within 2 years prior to the first dose, histologically distinct from the cancer under study, except for carcinoma in situ of the cervix, superficial non-invasive bladder cancer, or adequately treated stage I non-melanoma skin cancer.
- Prior treatment with KRAS G12C inhibitors, KRAS G12D inhibitors, pan-KRAS/pan RAS inhibitors, or other agents of the same class.
- Women who are pregnant or breast-feeding.
- Participants who have progressive disease or recurrence during neoadjuvant or adjuvant treatment, or within 6 months after the last dose of medication.
