JAB-21822 in Combination With Cetuximab in Patients With Advanced CRC and Other Solid Tumors With KRAS G12C Mutation

A Phase Ib/II Trial of JAB-21822 in Combination With Cetuximab in Patients With Advanced Colorectal Cancer, Small Intestine Cancer and Appendiceal Cancer With KRAS G12C Mutation

This study is to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of JAB-21822 in combination with cetuximab in patients with advanced colorectal cancer，advanced small intestine cancer and advanced appendiceal cancer with KRAS p.G12C mutation.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Colorectal Cancer; Small Intestinal Cancer; Appendiceal Cancer
• Intervention / Treatment: Drug: JAB-21822; Drug: Cetuximab

Detailed Description

The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 in combination with cetuximab to determine the MTD and RP2D during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-21822 is administered in combination with cetuximab during Dose Expansion phase in patients with advanced colorectal cancer，advanced small intestine cancer and advanced appendiceal cancer with KRAS p.G12C mutation.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Research site31
    • Beijing, Beijing Municipality, China, 100101
      • Research site01
    • Beijing, Beijing Municipality, China, 100101
      • Research site02
    • Beijing, Beijing Municipality, China, 100101
      • Research site12
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Research site13
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Research site06
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Research site05
    • Zhengzhou, Henan, China, 450000
      • Research site07
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Research site18
  • Hunan
    • Changsha, Hunan, China, 410000
      • Research site11
    • Changsha, Hunan, China, 410000
      • Research site29
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Research site09
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • Research site08
  • Shandong
    • Linyi, Shandong, China, 276002
      • Research site16
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Research site28
  • Shanxi
    • Xi’an, Shanxi, China, 710000
      • Research site23
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Research site19

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be able to provide an archived tumor sample
• Histologically or cytologically confirmed advanced colorectal cancer, advanced small intestinal cancer and advanced appendiceal cancer with KRAS p.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 metastases, except if treated and no evidence of radiographic progression or hemorrhage for at least 28 days
• Active infection requiring systemic treatment within 14 days
• Active HIV, HBV or HCV
• Any severe and/or uncontrolled medical conditions
• LVEF<50% assessed by ECHO
• QT interval >470 msec

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b Dose Escalation; Dose escalation of JAB-21822 to determine maximum tolerated dose of JAB-21822 in combination with cetuximab.	Drug: JAB-21822; JAB-21822 administered orally as a tablet.; Drug: Cetuximab; Cetuximab administered as an intravenous (IV) infusion.
Experimental: Phase 2 Dose Expansion, Cohort 1; Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.	Drug: JAB-21822; JAB-21822 administered orally as a tablet.; Drug: Cetuximab; Cetuximab administered as an intravenous (IV) infusion.
Experimental: Phase 2 Dose Expansion, Cohort 2; Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced small intestinal cancer and advanced appendiceal cancer.	Drug: JAB-21822; JAB-21822 administered orally as a tablet.; Drug: Cetuximab; Cetuximab administered as an intravenous (IV) infusion.

What is the study measuring?

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 (TRAE) or abnormal laboratory values assessment during the first 21 days of (Cycle 1) and excludes events that are deemed clearly related to underlying disease, progression, or intercurrent illness.	At the end of Cycle 1 (each cycle is 21 days)
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax)	Cmax of JAB-21822 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 will be measured by using plasma PK samples.	Up to 4 years
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
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
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 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

Collaborators and Investigators

• Sponsor: Allist Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Shen Lin Master of medicine, Peking University Cancer Hospital & Institute

Publications and helpful links

General Publications

• Li J, Wang Z, Huang J, Ba Y, Cao B, Luo S, Li W, Bai C, Song Z, Xiong J, Zhu L, An G, Zhang Y, Li Z, Li Y, Gu Y, Hu C, Li X, Huang C, Fu Q, Yin X, Liang X, Zhong D, Shi H, Li X, Li Z, Liu L, Wang F, Liang R, Xia G, Wang Z, Wang-Gillam A, Ding Y, Rao Z, Pan W, Lu S, Sun X, Shen L. Glecirasib with or without cetuximab in previously treated locally advanced or metastatic colorectal cancer with KRASG12C mutation (JAB-21822-1002 and JAB-21822-1007): two open-label, non-randomised phase 1/2 trials. Lancet Gastroenterol Hepatol. 2026 Feb;11(2):110-123. doi: 10.1016/S2468-1253(25)00267-5. Epub 2025 Dec 1.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Actual): April 30, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 27, 2021
• First Submitted That Met QC Criteria: January 4, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 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; Cecal Neoplasms; Cecal Diseases; Appendiceal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cetuximab
• Other Study ID Numbers: JAB-21822-1007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No