Phase 1/2a Study Of JAB-21822 Plus JAB-3312 In Patients With Advanced Solid Tumors Harboring KRAS P.G12C Mutation

Study Overview

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

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.

N/A

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

DRUG: JAB-21822
DRUG: JAB-3312

JAB-21822-1006

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-03-11	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-03
First Submitted that Met QC Criteria 2022-03-11	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-04
First Posted (ACTUAL) 2022-03-21	Results First Posted N/A	Last Verified 2025-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Dose escalation	DRUG: JAB-21822 KRAS G12C inhibitor DRUG: JAB-3312 SHP2 inhibitor
EXPERIMENTAL: Dose expansion	DRUG: JAB-21822 KRAS G12C inhibitor DRUG: JAB-3312 SHP2 inhibitor

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Dose escalation

DRUG: JAB-21822

KRAS G12C inhibitor

DRUG: JAB-3312

SHP2 inhibitor

EXPERIMENTAL: Dose expansion

DRUG: JAB-21822

KRAS G12C inhibitor

DRUG: JAB-3312

SHP2 inhibitor

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Number of participants with AEs	All patients participating in this study will be assessed for incidence and severity of AEs and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imagings and ophthalmological assessments	Approximately 2 years
Objective response rate (ORR)	ORR is defined as the proportion of participants with confirmed complete response or partial response	Approximately 2 years
Progression-free survival (PFS)	Period of time from the start of treatment to tumor progression or death from any cause (whichever occurs first) based on RECIST v1.1	Approximately 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Shanghai Allist Pharmaceuticals Co., Ltd Shanghai Allist Pharmaceuticals Co., Ltd

Phone Number: 021-80423288

Email: zhenhua.gong@allist.com.cn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Wang Wang Jie M.D., Peking University Cancer Hospital & Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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