JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation

Study Overview
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Brief Summary
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This study is to evaluate the safety and tolerability of JAB-21822 monotherapy and combination therapy in adult participants with advanced solid tumors harboring KRAS G12C mutation.

Detailed Description
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The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 monotherapy to determine the MTD and PR2D during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-21822 administered alone and combination with cetuximab during Dose Expansion phase in adult participants with advanced solid tumors harboring KRAS G12C mutation.

Official Title
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A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-21822 Monotherapy and Combination Therapy in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation

Conditions
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Advanced Solid Tumor, NSCLC, CRC

Intervention / Treatment
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* Drug: JAB-21822 (KRAS G12C inhibitor)
* Drug: JAB-21822 (KRAS G12C inhibitor)
* Drug: JAB-21822 (KRAS G12C inhibitor)
* Drug: Cetuximab (EGFR inhibitor)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be able to provide an archived tumor sample Histologically or cytologically confirmed solid tumors with KRAS G12C mutation Must have received at least 1 prior standard therapy Must have at least 1 measurable lesion per RECIST v1.1 Must have adequate organ function Must be able to swallow and retain orally administered medication Exclusion Criteria: Has brain or spinal metastases, except if treated and no evidence of radiographic progression or hemorrhage for at least 28 days Active infection requiring systemic treatment within 7 days Active HBV or HCV Any severe and/or uncontrolled medical conditions LVEF ≤50% assessed by ECHO or QTcF QT interval >470 msec Experiencing unresolved CTCAE 5.0 Grade >1 toxicities

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: Arm A0, JAB-21822 monotherapy, Phase 1, Dose Escalation<br>Dose escalation of JAB-21822 will be administered alone to determine the MTD and RP2D | Drug: JAB-21822 (KRAS G12C inhibitor)<br>* Administered orally<br>|
| Experimental: Arm A1, JAB-21822 monotherapy, Phare 2, Dose Expansion<br>JAB-21822 will be administered alone at RP2D in selected cancer type patients to evaluate the preliminary antitumor activity. | Drug: JAB-21822 (KRAS G12C inhibitor)<br>* Administered orally<br>|
| Experimental: Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion<br>JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity. | Drug: JAB-21822 (KRAS G12C inhibitor)<br>* Administered orally<br>Drug: Cetuximab (EGFR inhibitor)<br>* Administered IV<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) |  | At the end of Cycle 1 (each cycle is 21 days) | 
| Dose Escalation and 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 4 years | 
| Dose Expansion phase: Overall 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 4 years - from baseline to RECIST confirmed Progressive Disease | 
| 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 CTCAE v1.1 or death due to any cause, whichever occurs first. | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax) | Cmax of JAB-21822 alone or JAB-21822 plus cetuximabn will be measured by using plasma PK samples | Up to 4 years | 
| Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC) | AUC of JAB-21822 alone or JAB-21822 plus cetuximab will be measured by using plasma PK samples | Up to 4 years | 
| Dose Escalation phase: Overall response rate (ORR) | The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1. | Up to 4 years - from baseline to RECIST confirmed Progressive Disease | 
| Dose Escalation 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 CTCAE v1.1 or death due to any cause, whichever occurs first. | Up to 4 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 CTCAE v1.1 | Up to 4 years | 
| 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 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