A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1

Study Overview
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Brief Summary
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Evaluate the safety and tolerability, drug levels, and clinical activity of JAB-21822 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors with KRAS p.G12C mutation and a serine/threonine kinase 11 (STK11) co-mutation.

Detailed Description
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The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 during Dose Escalation phase and preliminary antitumor activity in patients with NSCLC with concurrent KRAS G12C mutant and STK11 mutant and KEAP wild type either treatment naïve or at least one line prior therapy for advance disease during the expansion phase..

Official Title
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A Phase Ib/II ,Single Arm, Multi-Center, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of JAB-21822 in Advanced or Metastatic Non-small Cell Lung Cancer With a KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: JAB 21822


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically documented, locally-advanced or metastatic NSCLC with KRAS p.G12C mutation identified through molecular testing. STK11 co-mutation and KEAP1 Wild-Type (local confirmation) Treatment naïve or have received at least 1 prior standard therapy for advanced NSCLC ECOG 0-1 Exclusion Criteria: Has CNS metastases or carcinomatous meningitis, except treated CNS metastases with no evidence of radiographic progression or hemorrhage for at least 28 days Any severe and/or uncontrolled medical conditions Active infection requiring systemic treatment within 7 days Therapeutic radiation therapy within 3 weeks of study day 1

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 ,Dose Exploration ,monotherapy<br>Dose escalation of JAB21822 will be administered as monotherapy to determine the MTD and RP2D | Drug: JAB 21822<br>* Administered orally<br>|
| Experimental: Phase 2, Dose Expansion, Part1 monotherapy<br>Part 1 dose expansion is to evaluate the safety and clinical activity of JAB-21822 at RP2D in subjects with previously untreated advanced non-small cell lung cancer (NSCLC) | Drug: JAB 21822<br>* Administered orally<br>|
| Experimental: Phase 2 Dose Expansion, Part 2 monotherapy<br>Part 2 dose expansion is to evaluate the safety and clinical activity of JAB-21822 at RP2D in subjects who had received at least one previous line of systemic therapy for NSCLC | Drug: JAB 21822<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation phase Number of participants with dose limiting toxicities (DLTs) | A DLT is defined as the clinically significant treatment-related adverse event or abnormal laboratory values assessment during the first 21 days of Cycle 1. It excludes adverse events (AEs) that are deemed clearly related to underlying disease, progression, or intercurrent illness. | At the end of Cycle 1 (each cycle is 21 days) | 
| Dose Escalation phase: Number of participants with adverse events | Patients will be assessed for incidence and severity of AEs according to NCI-CTCAE 5.0 criteria | Up to 3 years | 
| Dose Expansion phase: Objective response rate (ORR) | ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1 | Up to 3 years - from baseline to confirmed Progressive Disease per RECIST. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation phase: Objective response rate (ORR) | ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1 | Up to 3 years - from baseline to RECIST confirmed Progressive Disease | 
| Dose Escalation and Dose Expansion phase: Progression-free survival (PFS) | PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression per RECIST1.1 or death whichever occurs first | Up to 3 years | 
| Dose Escalation and Dose Expansion phase: Duration of response (DOR) | DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. | Up to 3 years | 
| Dose Escalation and Dose Expansion phase: Disease Control Rate (DCR) | DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1 | Up to 3 years | 
| Dose Escalation and Dose Expansion phase: Overall Survival (OS) | Defined as time from first treatment to death by any cause | Up to 3 years | 
| Dose Escalation and Dose Expansion phase: Time to response (TTR) | Defined as time from first treatment to first evidence of PR or CR | Up to 3 years | 
| Dose Expansion phase: Number of participants with adverse events | Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria | Up to 3 years | 
| Dose Escalation and Dose Expansion phase: Plasma concentration (Cmax) | Cmax of JAB-21822 will be measured by using plasma PK samples | Up to 3 Years | 
| Dose Escalation and Dose Expansion phase: Time to achieve Cmax (Tmax) | Tmax of JAB-21822 will be measured by using plasma PK samples | Up to 3 Years | 
| Escalation and Dose Expansion phase：Area under the plasma concentration-time curve (AUC) | AUC of JAB-21822 will be measured by using plasma PK samples | Up to 3 Years |