Clinical trial NCT05288205: Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation
Official title: A Phase 1/2a Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of JAB-21822 in Combination With JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: KRAS P.G12C
Non-small Cell Lung Cancer
Colorectal Cancer
Pancreatic Ductal Carcinoma
Lead sponsor: Allist Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-21
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 outcomes:
measure: recommended phase-2 dose (RP2D).
timeFrame: Approximately 2 years
measure: Number of participants with dose limiting toxicities
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Number of participants with AEs
timeFrame: Approximately 2 years
measure: Objective response rate (ORR)
timeFrame: Approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Pecking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy Of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Captal Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Fuzhou
country: China
facility: Fujian cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: The first Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southem Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Cancer Hospital Chinese Academy Of medical Sciences Shenzhen Center
state: Guangdong
city: Ha'erbin
country: China
facility: Harbin Medical University Cancer Hospital-Mammary gland of internal
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hosipital Of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of Hust
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital Of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South Univesity
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shenyang
country: China
facility: The First Hospital Of China Medical University
state: Liaoning
city: Hohhot
country: China
facility: The Affilated Hospital of Inner Mongolia Medical University
state: Neimenggu
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: LinYi
country: China
facility: LinYi Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang School of Medicine
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Wang Wang Jie M.D.
role: PRINCIPAL_INVESTIGATOR
References: