A Study of JAB-21822 in Patients With KRAS p.G12C Mutated Pancreatic Cancer

Study Overview
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Brief Summary
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This study is to evaluate the efficacy and safety of JAB-21822 monotherapy in adult participants with KRAS G12C mutated pancreatic cancer

Detailed Description
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This is a single-arm, open-label, multicenter phase 2 study to evaluate the efficacy and safety of JAB-21822 monotherapy in adult participants with advanced KRAS p.G12C mutated pancreatic cancer.

Official Title
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A Phase 2, Multi-Center, Open-Label, Single-arm Study to Evaluate the Efficacy and Safety of JAB-21822 Monotherapy in Patients With Locally Advanced or Metastatic KRAS p.G12C Mutated Pancreatic Cancer

Conditions
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KRAS P.G12C, Pancreatic Cancer

Intervention / Treatment
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* Drug: JAB-21822


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically or cytologically confirmed pancreatic cancer with KRAS p.G12C mutation identified through molecular testing. Previously progressed on or after gemcitabine-based and/or FOFIRINOX/mFOFIRINOX chemotherapy, no more than 3 lines of prior systemic therapies. Participants with disease recurrence during or within 6 months after adjuvant therapy can be included. Participants with MSI-H/dMMR must experience anti-PD-1 therapy. Exclusion Criteria: Previously received a KRAS G12C inhibitor. History of interstitial lung disease, non-infectious pneumonia, or uncontrolled lung disease (including pulmonary fibrosis, acute lung disease, etc.). Uncontrolled pleural effusion, pericardial effusion, or ascites. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 electrocardiograms. Use of a drug with known risk of torsades de points (TdP) within 14 days prior to the first dose. Cannot discontinue a proton pump inhibitor (PPI) or H2 receptor blocker within 3 days or 5 half-lives (whichever is longer) prior to the first dose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JAB-21822<br>Monotherapy | Drug: JAB-21822<br>* 800mg, orally QD with 21 days each cycle, treatment till disease progression or intolerable toxicity or withdraw for other reasons<br>* Other names: Glecirasib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) by independent central radiological review (IRC) according to RECIST 1.1. | ORR is defined as the proportion of participants with confirmed complete response or partial response by IRC according to RECIST 1.1. | Approximately 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) | DOR is defined as the time from date of the first objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first. | Approximately 1.5 years | 
| Time to response (TTR) by IRC according to RECIST 1.1 | TTR is defined as the duration of time between the date of the first dose and the date of first documented response of either CR or PR. | Approximately 1.5 years | 
| Progression-free survival (PFS) by IRC according to RECIST 1.1 | PFS is defined as time from the first dose until disease progression or death from any cause, whichever occurs first. | Approximately 1.5 years | 
| Disease control rate (DCR) by IRC according to RECIST 1.1 | DCR is defined as the proportion of participants with BOR of CR or PR or stable disease (SD) | Approximately 1.5 years | 
| CA19-9 response rate | CA19-9 response rate is defined as the proportion of participants with CA19-9 response (achieving ≥50% decrease in CA19-9 serum levels). | Approximately 1.5 years | 
| Overall survival (OS) | OS is defined as time from date of the first dose to date of death due to any cause. | Approximately 2.0 years | 
| Number of participants with adverse events | Participants will be assessed for incidence and severity of AEs according to NCI-CTCAE 5.0 criteria | Approximately 1.5 years |