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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 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
Exclusion Criteria:
* 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
Primary outcome measure(s)
recommended phase-2 dose (RP2D). — Approximately 2 years RP2D should be selected based on a comprehensive assessment of maximum tolerated dose(MTD), toxicity, pharmacokinetic(PK) profile, and efficacy data.
Number of participants with dose limiting toxicities — Approximately 2 years 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.
Trial sites (27)
Facility
City
Region
Status
The First Affiliated Hospital of USTC Anhui Provincial Hospital
Hefei
Anhui
Not Yet Recruiting
Pecking Union Medical College Hospital
Beijing
Beijing Municipality
Not Yet Recruiting
Cancer Hospital Chinese Academy Of Medical Sciences
Beijing
Beijing Municipality
Recruiting
Beijing Tiantan Hospital, Captal Medical University
Beijing
Beijing Municipality
Not Yet Recruiting
Beijing Cancer Hospital
Beijing
Beijing Municipality
Recruiting
Peking University Third Hospital
Beijing
Beijing Municipality
Recruiting
Beijing Chest Hospital, Capital Medical University
Beijing
Beijing Municipality
Not Yet Recruiting
Fujian cancer Hospital
Fuzhou
Fujian
Not Yet Recruiting
The First Affiliated Hospital Xiamen University
Xiamen
Fujian
Not Yet Recruiting
The first Affiliated Hospital, Sun Yat-sen University
Guangzhou
Guangdong
Not Yet Recruiting
Zhujiang Hospital of Southem Medical University
Guangzhou
Guangdong
Not Yet Recruiting
Cancer Hospital Chinese Academy Of medical Sciences Shenzhen Center
Shenzhen
Guangdong
Not Yet Recruiting
Harbin Medical University Cancer Hospital-Mammary gland of internal
Harbin
Heilongjiang
Not Yet Recruiting
Henan Cancer Hospital
Zhengzhou
Henan
Not Yet Recruiting
The First Affiliated Hosipital Of Zhengzhou University
Zhengzhou
Henan
Not Yet Recruiting
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan
Hubei
Not Yet Recruiting
Tongji Hospital Tongji Medical College of Hust
Wuhan
Hubei
Not Yet Recruiting
Renmin Hospital Of Wuhan University
Wuhan
Hubei
Not Yet Recruiting
Xiangya Hospital Central South Univesity
Changsha
Hunan
Not Yet Recruiting
Hunan Cancer Hospital
Changsha
Hunan
Not Yet Recruiting
The First Hospital Of China Medical University
Shenyang
Liaoning
Not Yet Recruiting
The Affilated Hospital of Inner Mongolia Medical University
Hohhot
Neimenggu
Not Yet Recruiting
Qilu Hospital of Shandong University
Jinan
Shandong
Not Yet Recruiting
Shandong Cancer Hospital
Jinan
Shandong
Not Yet Recruiting
LinYi Cancer Hospital
Linyi
Shandong
Not Yet Recruiting
Fudan University Shanghai Cancer Center
Shanghai
Shanghai Municipality
Not Yet Recruiting
The Second Affiliated Hospital Zhejiang School of Medicine
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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