FIH Study of JAB-21822 in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation in China

Study Overview
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Brief Summary
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To assess safety, tolerability, PK, preliminary efficacy and determine recommended phase 2 dose (RP2D) of JAB-21822 administered in adult participants with KRAS p.G12C-mutant advanced solid tumors.

Detailed Description
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This is a phase 1/2a, first-in-human, open-label study of JAB-21822, this study has two parts: dose escalation phase and dose expansion phase.

Official Title
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Multi-center, Open, Dose-escalation, and Expanded Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of JAB-21822 in Advanced Solid Tumors With KRAS p.G12c Mutations

Conditions
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CRC, NSCLC, Solid Tumor

Intervention / Treatment
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* Drug: JAB-21822
* Drug: JAB-21822


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Advanced (metastatic or unresectable) KRAS G12C mutant solid tumors, with failure or absence of standard treatment Subject must be ≥18 years Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. Subjects with life expectancy ≥3 months. Subjects must have at least one measurable lesion as defined by RECIST v1.1. There was no serious organ dysfunction in the screening stage Male or female subjects of reproductive age agree to use adequate contraception Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer Previously treated with KRAS G12C inhibitor Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV) Impaired heart function or clinically significant heart disease Pregnant or breast-feeding Previous allogeneic bone marrow transplant or organ transplant Intended study subjects who were unable to abstain from alcohol during medication Other unqualified conditions judged by the investigators

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<br>Dose escalation of JAB-21822 to determine maximum tolerated dose | Drug: JAB-21822<br>* JAB-21822 will be administered orally<br>|
| Experimental: Phase 1 Dose Expansion<br>Conditionally required | Drug: JAB-21822<br>* JAB-21822 will be administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLTs) in the dose escalation phase | Number of participants with dose limiting toxicities | first 21 days | 
| 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 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Cmax of JAB-21822 will be measured by using plasma PK samples | up to 4 years | 
| Area under plasma concentration versus time curve (AUC) |  | up to 4 years | 
| Objective response rate ( ORR ) | ORR is defined as the proportion of participants with complete response or partial response (CR+PR) per RECIST v 1.1 | up to 4 years | 
| Duration of response ( DOR ) | DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first. | up to 4 years | 
| Disease Control Rate ( DCR ) | DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease(SD) per CTCAE v1.1 | up to 4 years | 
| 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 CTCAE v1.1 or death which occurs first | up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KRAS G12C Mutant Advanced Solid Tumor; NSCLC; CRC