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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05288205
• Other study ID #: JAB-21822-1006
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 14, 2022
• Est. completion date: March 2026

Study information

• Verified date: June 2022
• Source: Jacobio Pharmaceuticals Co., Ltd.
• Contact: Jacobio Pharmaceuticals
• Phone: 86 10 56315466
• Email: clinicaltrials[@]jacobiopharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 124
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 who have failed or lack standard-of-care (SOC) or are unwilling to undergo or intolerant to SOC; those with solid tumors harboring KRAS p.G12C mutation are preferred;
• 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 conformed 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

Related Conditions & MeSH terms

• Carcinoma, Ductal
• Carcinoma, Pancreatic Ductal
• Colorectal Cancer
• Non-small Cell Lung Cancer
• Pancreatic Ductal Carcinoma

Intervention

Drug:
• JAB-21822
KRAS G12C inhibitor
• JAB-3312
SHP2 inhibitor

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Chest Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tiantan Hospital, Captal Medical University	Beijing	Beijing
China	Cancer Hospital Chinese Academy Of Medical Sciences	Beijing	Beijing
China	Pecking Union Medical College Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	Xiangya Hospital Central South Univesity	Changsha	Hunan
China	West China Hospital Sichuan University	Chendu	Sichuan
China	The Second Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian cancer Hospital	Fuzhou	Fujian
China	Harbin Medical University Cancer Hospital-Mammary gland of internal	Ha'erbin	Heilongjiang
China	The Affilated Hospital of Inner Mongolia Medical University	Hohhot	Neimenggu
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Shandong Cancer Hospital	Jinan	Shandong
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	The First Hospital Of China Medical University	Shenyang	Liaoning
China	Cancer Hospital Chinese Academy Of medical Sciences Shenzhen Center	Shenzhen	Guangdong
China	Renmin Hospital Of Wuhan University	Wuhan	Hubei
China	Tongji Hospital Tongji Medical College of Hust	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'An Jiaotong University	Xi'an	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Jacobio Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Objective response rate (ORR)	ORR is defined as the proportion of participants with confirmed complete response or partial response	Approximately 2 years
Secondary	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