JAB-21822 Combined With Chemotherapy and Bevacizumab in Second-line KRAS G12C CRC

A Phase Ib, Open Lable, Clinical Trial of JAB-21822 Combined With Second Line Chemotherapy and Bevacizumab for Metastatic Colorectal Cancer With KRAS G12C Mutation

KRAS is a common genetic mutation in tumors, and CRC is one of the tumors with a high KRAS mutation rate. The anti-tumor activity of KRAS G12C inhibitors combined with anti-EGFR anti-bodies have been proven in patients with advanced colorectal cancer, and one of them was approved for patients who have previously received standard treatment. However, Chinese patients still do not have access to these drugs. This study is to determine the efficacy and safety of KRAS G12C inhibitor JAB-21822 in combination with the second-line standard chemotherapy and bevacizumab in advanced colorectal cancer failed to standard therapy in Chinese population.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: JAB-21822; Drug: standard second-line chemotherapy; Drug: Bevacizumab

Detailed Description

The study is aimed for patients with histologically confirmed advanced metastatic colorectal cancer with KRAS G12C mutation, patients enrolled will treated with JAB-21822 combined with standard second-line chemotherapy and bevacizumab until disease progression or intolerable toxicity or patient-initiated withdrawal from the study. Enrolled patients will undergo imaging assessments at baseline and every 6 weeks during the treatment period, the anti-tumor efficacy will be evaluated by the investigator according to RECIST v1.1. Safety assessment included vital signs, haematology, blood biochemistry and urinalysis and will be monitored regularly during the study period during treatment. Any discomfort experienced by the patients after administration of the drug will also be recorded.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University First Hospital
  • Beijing, China
    • Beijing Cancer Hospital
  • Hohhot, China
    • Peking University Cancer Hospital (Inner Mongolia Campus)/Afffliated Cancer Hospital of Inner Mongolia Medical University
  • Shanghai, China
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically (or cytologically) confirmed, unresectable metastatic colorectal cancer.
• KRAS G12C mutation.
• At least one measurable disease per RECIST v1.1; assessed within 28 days before first dose.
• Subject have withdrawn from the first-line chemotherapy due to disease progression or unacceptable toxicity; if first-line chemotherapy and maintenance therapy were received, disease progression must within three months; first-line chemotherapy regimens do not limit the use of antiangiogenic agents.
• Adequate bone marrow, liver and renal function.
• ECOG performance status 0-1.
• Informed consent has been signed.

Exclusion Criteria:

• Patients have received KRAS G12C inhibitors.
• Patients have received a first-line treatment, which include fluoropyrimidine, oxaliplatin and irinotecan.
• Patients who are pregnant or breastfeeding.
• Life expectancy of less than 3 months.
• Patients who had major surgery or significant trauma within 4 weeks prior to the first blood sample collection during the screening period, or expected to require major surgery during the study period.
• Patients with active ulcers and gastrointestinal bleeding.
• Prior history of interstitial lung disease or non-infectious pneumonia; history of active tuberculosis.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Patients with clinically diagnosed autoimmune disease; HIV, HCV positive; HBV-DNA beyond the normal range of the laboratory; Acute CMV infection.
• Patients with active central nervous system metastases requiring treatment.
• Patients with other malignancies within five years.
• Assessed by the investigator, patients who are unable or unwilling to comply with the requirements of the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JAB-21822 and second-line standard chemotherapy with bevacizumab; Patients receive JAB-21822 combined with chemotherapy with bevacizumab as the second-line treatment until disease progression or intolerable toxicity	Drug: JAB-21822; Tablet, oral, 800 mg/QD, until PD or intolerable toxicity; Drug: standard second-line chemotherapy; The second line standard chemotherapy regimen recommended by clinical practice; Other Names: FOLFIRI, FOLFOX; Drug: Bevacizumab; 5mg/kg every two weeks (according to the assessment by investigator)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The percentage of patients with total number of Complete Response (CR) + total number of Partial Response (PR) per RECIST v1.1	Time Frame: up to 1year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined as the time from date of study treatment to death due to any cause.	Time Frame: up to 1 year
Progression-free Survival (PFS)	Defined as the time from date of study treatment to disease progression radiological/clinical or death due to any cause, whichever occurs first.	Time Frame: up to 1 year
Disease Control Rate (DCR)	Defined as the percentage of patients whose best response are not Progressive Disease (PD) according to RECIST v1.1.	Time Frame: up to 1 year
Duration of Response (DOR)	Defined as the time between the first assessment of the tumor as a CR or PR and the first assessment as disease progression (PD) or death from any cause.	Time Frame: up to 1 year
Rate of treatment-related adverse events	Number of patients with treatment-related adverse events as assessed by CTCAE v5.0.	Time Frame: up to 1 year

Collaborators and Investigators

• Sponsor: Jian Li
• Investigators: Study Director: Jacobio Pharmaceuticals, Jacobio Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: September 25, 2024
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 20, 2025

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; Folfox protocol
• Other Study ID Numbers: JAB-21822-CRC003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No