Metastatic Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
KRAS, KRAS mutation, KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12S, KRAS G12A,, Pan-KRAS, Pancreatic ductal adenocarcinoma, KRAS-mutant tumor, Targeted Therapy, JAB-23E73
Brief summary
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.
Detailed 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.
Interventions
DRUGJAB-23E73 tablet，nab-paclitaxel，gemcitabine
Orally, intravenous (IV) infusion
Sponsors
Jacobio Pharmaceuticals Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
1. Inability to swallow oral medications or the presence of gastrointestinal dysfunction or disease that may significantly alter drug absorption. 2. 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. 3. Prior treatment with KRAS G12C inhibitors, KRAS G12D inhibitors, pan-KRAS/pan RAS inhibitors, or other agents of the same class. 4. Women who are pregnant or breast-feeding. 5. Participants who have progressive disease or recurrence during neoadjuvant or adjuvant treatment, or within 6 months after the last dose of medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicities (DLT) | Up to 28 days | The number and proportion of participants who experienced dose-limiting toxicities (DLT). |
| Adverse events.safety evaluation | Up to approximately 3 years | The types, incidence, severity, and outcomes of adverse events and serious adverse events evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | Up to approximately 3 years | Objective response rate, ORR is defined as the proportion of participants with confirmed complete response or partial response |
| DOR | Up to approximately 3 years | Duration of response, DOR is defined as the time from the first documented CR or PR to the first occurrence of disease progression or death from any cause, whichever occurs first |
| TTR | Up to approximately 3 years | Time to Response, TTR is defined as the time from the first dose of study treatment to the first documented CR or PR. |
| PFS | Up to approximately 3 years | Progression-Free Survival , PFS is defined as the time from the first dose of study treatment to the first documented disease progression or death from any cause, whichever occurs first. |
| DCR | Up to approximately 3 years | Disease Control Rate, DCR is defined as the proportion of participants whose best overall response is CR, PR, or SD.. |
| OS | Up to approximately 3 years | Overall Survival , OS is defined as the time from the first dose of study treatment to death from any cause. |
| PK | Up to approximately 3 years | maximum plasma concentration (Cmax) |
Countries
China
Contacts
CONTACTJacobio Pharmaceuticals
STUDY_DIRECTORJacobio Pharmaceuticals
Jacobio Pharmaceuticals
Outcome results
None listed