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

Conditions

Advanced Colorectal Cancer, Appendiceal Cancer, Small Intestinal Cancer

Brief summary

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.

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.

Jiang L, Luo Y, Liang H, Feng X, Huang Y, Li Y, Wang Z, Xu T, Zou H, Li Z, Shen L, Chen Y, Wang W, Li J.

2026-07-01

10.1007/s13577-026-01405-0

Glecirasib with or without cetuximab in previously treated locally advanced or metastatic colorectal cancer with KRAS<sup>G12C</sup> mutation (JAB-21822-1002 and JAB-21822-1007): two open-label, non-randomised phase 1/2 trials.

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.

2025-12-01

10.1016/s2468-1253(25)00267-5

Glecirasib, a Potent and Selective Covalent KRAS G12C Inhibitor Exhibiting Synergism with Cetuximab or SHP2 Inhibitor JAB-3312

Peng Wang, Xin Sun, Xueting He, Di Kang, Xiaoyu Liu et al. (12 authors)

Cancer Research Communications2025-04-303 citations

10.1158/2767-9764.crc-25-0001

Efficacy and safety of glecirasib (JAB-21822) monotherapy and in combination with cetuximab in patients with KRAS G12C-mutated advanced colorectal cancer.

Jian Li, Jing Huang, Yi Ba, Baoshan Cao, Suxia Luo et al. (19 authors)

Journal of Clinical Oncology2025-01-276 citations

10.1200/jco.2025.43.4_suppl.191

Interventions

DRUGJAB-21822

JAB-21822 administered orally as a tablet.

DRUGCetuximab

Cetuximab administered as an intravenous (IV) infusion.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Dose Escalation phase: Number of participants with dose-limiting toxicities (DLTs)	At the end of Cycle 1 (each cycle is 21 days)	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.
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.

Secondary

Measure	Time frame	Description
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 Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax)	Up to 4 years	Cmax of JAB-21822 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 will be measured by using plasma PK samples.
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.
Dose Escalation phase: Overall response rate (ORR)	Up to 4 years	The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1.
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 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.

Countries

China

Contacts

PRINCIPAL_INVESTIGATORShen Lin Master of medicine

Peking University Cancer Hospital & Institute

Outcome results

None listed