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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor; NSCLC; CRC
• Interventions: Drug: JAB-21822 (KRAS G12C inhibitor); Drug: Cetuximab (EGFR inhibitor)

• Registration Number: NCT05002270
• Lead Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2021-07-26
• Study First Submitted QC: 2021-08-04
• Study First Posted: 2021-08-12
• Study Start: 2021-09-03
• Status Verified: 2022-10
• Last Update Submitted: 2023-09-06
• Last Update Posted: 2023-09-07
• Primary Completion: 2024-01
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm A0, JAB-21822 monotherapy, Phase 1, Dose Escalation	JAB-21822 (KRAS G12C inhibitor)	Dose escalation of JAB-21822 will be administered alone to determine the MTD and RP2D
Arm A1, JAB-21822 monotherapy, Phare 2, Dose Expansion	JAB-21822 (KRAS G12C inhibitor)	JAB-21822 will be administered alone at RP2D in selected cancer type patients to evaluate the preliminary antitumor activity.
Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion	JAB-21822 (KRAS G12C inhibitor)	JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity.
Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion	Cetuximab (EGFR inhibitor)	JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity.

Primary Outcome Measures

Name	Time	Method
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	Up to 4 years	Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria
Dose Expansion phase: Overall response rate (ORR)	Up to 4 years - from baseline to RECIST confirmed Progressive Disease	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1
Dose Expansion phase: Duration of response ( DOR )	Up to 4 years	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.

Secondary Outcome Measures

Name	Time	Method
Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax)	Up to 4 years	Cmax of JAB-21822 alone or JAB-21822 plus cetuximabn will be measured by using plasma PK samples
Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC)	Up to 4 years	AUC of JAB-21822 alone or JAB-21822 plus cetuximab will be measured by using plasma PK samples
Dose Escalation phase: Overall response rate (ORR)	Up to 4 years - from baseline to RECIST confirmed Progressive Disease	The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1.
Dose Escalation phase: Duration of response ( DOR )	Up to 4 years	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.
Dose Escalation and Dose Expansion phase: Disease Control Rate ( DCR )	Up to 4 years	DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease(SD) per CTCAE v1.1
Dose Escalation and Dose Expansion phase: Progression-free survival (PFS)	Up to 4 years	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

Trial Locations

Locations (2)

Mayo Clinc; 🇺🇸 Jacksonville, Florida, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States