Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation

NCT05288205 | Recruiting Phase 1

• 1 other identifier: JAB-21822-1006
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 27

Brief Summary

This is a multicenter, open-label phase 1/2a study consisting of two parts: dose escalation phase and dose expansion phase. The objective of the dose escalation phase is to evaluate the safety, tolerability and pharmacokinetics of JAB-21822 in combination with JAB-3312 in patients with advanced solid tumors harboring KRAS p.G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion phase, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS p.G12C mutation.

Conditions

KRAS P.G12C; Non-small Cell Lung Cancer; Colorectal Cancer; Pancreatic Ductal Carcinoma

Outcome Measures

Primary Outcomes (2)

• recommended phase-2 dose (RP2D).

  RP2D should be selected based on a comprehensive assessment of maximum tolerated dose(MTD), toxicity, pharmacokinetic(PK) profile, and efficacy data.

  Approximately 2 years

• Number of participants with dose limiting toxicities

  Dose-limiting toxicity (DLT) is defined as an adverse event (AE) or clinically significant abnormal laboratory value occurring in Cycle 1 (DLT assessment period), which is unrelated to progressive disease, concurrent disease, or concomitant medication but related to JAB-21822 and/or JAB-3312, and meets the criteria for DLT.

  Approximately 2 years

Secondary Outcomes (3)

• Number of participants with AEs

  Approximately 2 years

• Objective response rate (ORR)

  Approximately 2 years

• Progression-free survival (PFS)

  Approximately 2 years

Study Arms (2)

Dose escalation

EXPERIMENTAL

Drug: JAB-21822; Drug: JAB-3312

Dose expansion

EXPERIMENTAL

Drug: JAB-21822; Drug: JAB-3312

Interventions

JAB-21822 DRUG

KRAS G12C inhibitor

Dose escalation; Dose expansion

JAB-3312 DRUG

SHP2 inhibitor

Dose escalation; Dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A written informed consent should be signed by a subject or his/her legal representative before any study-related procedures are performed;
• Subjects with histologically or cytologically confirmed locally advanced or metastatic advanced solid tumors harboring KRAS p.G12C mutation who have failed or lack standard-of-care (SOC) or are unwilling to undergo or intolerant to SOC;
• Expected survival ≥ 3 months;
• Subjects must have at least one measurable lesion as defined by RECIST v1.1. If no measurable lesion untreated with radiation is selected as the target lesion, a lesion treated with radiation ≥ 4 weeks before the first dose and with progression confirmed by radiography may be selected as the target lesion;
• Eastern Cooperative Oncology Group(ECOG) performance status 0-1;
• The organ functions of subjects meet the criteria for the following laboratory parameters at screening;
• Subjects must be able to swallow oral medications without gastrointestinal abnormalities that significantly affect drug absorption

You may not qualify if:

• Patients with previous (≤ 3 years) or current tumors of other pathological types, except for cured cervical carcinoma in situ, ductal carcinoma in situ of the breast, prostatic intraepithelial neoplasia, superficial non-invasive bladder cancer, stage I skin cancer (except melanoma); subjects without recurrence or metastasis for \> 3 years after treatment, without current evidence of tumor, and without significant risk of recurrence of previous malignant diseases in the opinion of the study doctor may also be enrolled;
• Serious allergy to the investigational drug or excipients (such as microcrystalline cellulose, etc.);
• Patients with previous (≤ 6 months before the initiation of treatment) or current severe autoimmune diseases (including adverse reactions caused by previous anti- tumor immunotherapies), or autoimmune diseases requiring long-term systemic hormone therapy at immunosuppressive dose levels (prednisone \> 10 mg/day or equivalent drugs);
• HIV, hepatitis B virus(HBV), or hepatitis C virus(HCV) positive;
• Previous (≤ 6 months prior to the first dose) or current evidence of the following diseases: acute myocardial infarction, unstable angina and cerebrovascular accident;
• Subjects who have impaired cardiac functions or clinically significant cardiac diseases;
• Pregnant or lactating women

Sponsors & Collaborators

• Allist Pharmaceuticals, Inc.: lead

Study Sites (27)

The First Affiliated Hospital of USTC Anhui Provincial Hospital

Hefei, Anhui, 230001, China

NOT YET RECRUITING

Pecking Union Medical College Hospital

Beijing, Beijing Municipality, 100005, China

NOT YET RECRUITING

Cancer Hospital Chinese Academy Of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Beijing Tiantan Hospital, Captal Medical University

Beijing, Beijing Municipality, 100070, China

NOT YET RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

Beijing Chest Hospital, Capital Medical University

Beijing, Beijing Municipality, 101125, China

NOT YET RECRUITING

Fujian cancer Hospital

Fuzhou, Fujian, 350014, China

NOT YET RECRUITING

The First Affiliated Hospital Xiamen University

Xiamen, Fujian, 361003, China

NOT YET RECRUITING

The first Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

NOT YET RECRUITING

Zhujiang Hospital of Southem Medical University

Guangzhou, Guangdong, 510280, China

NOT YET RECRUITING

Cancer Hospital Chinese Academy Of medical Sciences Shenzhen Center

Shenzhen, Guangdong, 518116, China

NOT YET RECRUITING

Harbin Medical University Cancer Hospital-Mammary gland of internal

Harbin, Heilongjiang, 150081, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

NOT YET RECRUITING

The First Affiliated Hosipital Of Zhengzhou University

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

NOT YET RECRUITING

Tongji Hospital Tongji Medical College of Hust

Wuhan, Hubei, 430030, China

NOT YET RECRUITING

Renmin Hospital Of Wuhan University

Wuhan, Hubei, 430060, China

NOT YET RECRUITING

Xiangya Hospital Central South Univesity

Changsha, Hunan, 410008, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

NOT YET RECRUITING

The First Hospital Of China Medical University

Shenyang, Liaoning, 110001, China

NOT YET RECRUITING

The Affilated Hospital of Inner Mongolia Medical University

Hohhot, Neimenggu, 750306, China

NOT YET RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

NOT YET RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

NOT YET RECRUITING

LinYi Cancer Hospital

Linyi, Shandong, 276002, China

NOT YET RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

NOT YET RECRUITING

The Second Affiliated Hospital Zhejiang School of Medicine

Hangzhou, Zhejiang, 310009, China

NOT YET RECRUITING

Related Publications (2)

• Zhong J, Zhao J, Duan J, Fang J, Fei K, Li X, Chen J, Wang Z, Chu Q, Yu Y, Liu Z, Zhang L, Zhao Y, Li X, Wu L, Xing L, Zhuang W, Fang X, Chang J, Pan Y, Dong X, Liu L, Bai C, Pan P, Song Q, Jin B, Cao B, Ye F, Shi J, Tang K, Wang-Gillam A, Ding Y, Bi C, Shao Y, Pang J, Wan R, Sun B, Xu J, Wang J; JAB-21822-1006 Study Group. Glecirasib plus sitneprotafib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 1/2a trial. Lancet Respir Med. 2025 Nov 28:S2213-2600(25)00258-9. doi: 10.1016/S2213-2600(25)00258-9. Online ahead of print.

  PMID: 41325755 DERIVED

• Kang D, Wang Y, Lin Y, Ma WW, Morgensztern D, Leventakos K, Bi C, Ding Y, Xiong J, Yan M, Sun X, Wang P, Ma C, Wang Y. JAB-3312, a Potent Allosteric SHP2 Inhibitor That Enhances the Efficacy of RTK/RAS/MAPK and PD-1 Blockade Therapies. Clin Cancer Res. 2025 Jul 15;31(14):3019-3032. doi: 10.1158/1078-0432.CCR-24-3691.

  PMID: 40333694 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Carcinoma, Pancreatic Ductal

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Wang Wang Jie M.D.

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shanghai Allist Pharmaceuticals Co., Ltd Shanghai Allist Pharmaceuticals Co., Ltd

CONTACT

021-80423288; zhenhua.gong@allist.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 21, 2022
• Study Start: April 14, 2022
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (27)