A Study of JAB-21822 in Adult Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation in China

Multi-center, Open, Dose-escalation, and Expanded Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of JAB-21822 in Advanced Solid Tumors With KRAS p.G12C Mutation

To assess safety, tolerability, PK, efficacy and determine recommended phase 2 dose (RP2D) of JAB-21822 (glecirasib) administered in adult participants with KRAS p.G12C-mutant advanced solid tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC; Solid Tumor
• Intervention / Treatment: Drug: JAB-21822

Detailed Description

This is a phase 1/2a, first-in-human, open-label study of JAB-21822, this study has two parts: dose escalation phase and dose expansion phase.

• Study Type: Interventional
• Enrollment (Actual): 315
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent
2. Advanced (metastatic or unresectable) KRAS p.G12C mutant solid tumors, with failure or absence of standard treatment
3. Subject must be ≥18 years
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
5. Subjects with life expectancy ≥3 months.
6. Subjects must have at least one measurable lesion as defined by RECIST v1.1.
7. There was no serious organ dysfunction in the screening stage
8. Male or female subjects of reproductive age agree to use adequate contraception

Exclusion Criteria:

1. History of intestinal disease or major gastric surgery or inability to swallow oral medications
2. Other active cancer
3. Previously treated with KRAS G12C inhibitor
4. Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
5. Impaired heart function or clinically significant heart disease
6. Pregnant or breast-feeding
7. Previous allogeneic bone marrow transplant or organ transplant
8. Intended study subjects who were unable to abstain from alcohol during medication
9. Other unqualified conditions judged by the investigators

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 1 Dose Exploration; Dose escalation of JAB-21822 to determine maximum tolerated dose.	Drug: JAB-21822; JAB-21822 will be administered orally; Other Names: glecirasib
Experimental: Phase IIa Dose Expansion; Patients with KRAS p.G12C mutant advanced non small cell lung cancer or other solid tumors will be enrolled and treated at the monotherapy RP2D to evaluate the safety and preliminary efficacy.	Drug: JAB-21822; JAB-21822 will be administered orally; Other Names: glecirasib
Experimental: Phase IIb; Patients with KRAS p.G12C mutant advanced non small cell lung cancer will be enrolled and treated at the monotherapy RP2D to evaluate the safety and efficacy.	Drug: JAB-21822; JAB-21822 will be administered orally; Other Names: glecirasib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicities (DLTs) in the dose escalation phase	Number of participants with dose limiting toxicities	first 21 days
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 3 years
Overall response rate (ORR) by IRC (independent review committee)	ORR is defined as the proportion of participants with complete response and partial response (CR+PR) per RECIST v 1.1	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) by investigator	ORR is defined as the proportion of participants with complete response and partial response (CR+PR) per RECIST v 1.1	up to 3 years
Duration of response ( DOR )	DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first.	up to 3 years
Disease Control Rate ( DCR )	DCR is defined as percentage of participants with complete response (CR), partial response (PR), and stable disease(SD) per RECIST v1.1	up to 3 years
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 or death per RECIST v1.1, which occurs first	up to 3 years
Time to response (TTR)	Time from patient randomization (first treatment) to first response per RECIST 1.1 criteria	up to 3 years
Peak Plasma Concentration (Cmax)	Cmax of JAB-21822 will be measured by using plasma PK samples	up to 3 years

Collaborators and Investigators

• Sponsor: Allist Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Li J, Deng T, Gu Y, Calles Blanco A, Li Z, Bai C, Wu L, Huang J, Li X, Yao Y, Song Z, Li Y, Liu L, Xing L, Wu W, Martinez-Perez J, Hubert A, Zugazagoitia J, Zhang J, Wang Y, Zhao Y, Wen G, Xia G, Zhong D, Chen X, Jiang K, Wang-Gillam A, Ding Y, Liu S, Rao Z, Liu X, Shen L. Efficacy and safety of glecirasib in solid tumors with KRAS G12C mutation: A pooled analysis of two phase I/II trials. Cancer Commun (Lond). 2025 Nov;45(11):1500-1512. doi: 10.1002/cac2.70056. Epub 2025 Oct 2.
• 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.
• Shi Y, Fang J, Xing L, Yao Y, Zhang J, Liu L, Wang Y, Hu C, Xiong J, Liu Z, Yang R, Wang Z, Zhao E, Wang M, Zhao Y, Tang K, Li Z, Song Z, Li Y, Zhuang W, Jin B, Cheng Y, Hu Y, Gu Y, Wu L, Ma R, Yu Q, Yu Y, Zhao J, Zhao H, Lv D, Shang Y, Xing P, Zhou J, Li X, Liu Z, Dai Z, Xia G, Chen X, Ba Y, Bai C, Li Q, An G, Hu W, Wang Y, Wang-Gillam A, Ding Y, Li Q, Rao Z. Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial. Nat Med. 2025 Mar;31(3):894-900. doi: 10.1038/s41591-024-03401-z. Epub 2025 Jan 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: KRAS p.G12C Mutant Advanced Solid Tumor; NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: JAB-21822-1002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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