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

Phase 1

Recruiting

• Conditions: Non-small Cell Lung Cancer; KRAS P.G12C; Colorectal Cancer; Pancreatic Ductal Carcinoma
• Interventions: Drug: JAB-21822; Drug: JAB-3312

• Registration Number: NCT05288205
• Lead Sponsor: Jacobio Pharmaceuticals Co., Ltd.

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-03-11
• Study First Submitted QC: 2022-03-11
• Study First Posted: 2022-03-21
• Study Start: 2022-04-14
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-29
• Last Update Posted: 2022-06-30
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 124

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation	JAB-3312	-
Dose expansion	JAB-3312	-
Dose expansion	JAB-21822	-
Dose escalation	JAB-21822	-

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
Number of participants with AEs	Approximately 2 years	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
Objective response rate (ORR)	Approximately 2 years	ORR is defined as the proportion of participants with confirmed complete response or partial response
Progression-free survival (PFS)	Approximately 2 years	Period of time from the start of treatment to tumor progression or death from any cause (whichever occurs first) based on RECIST v1.1

Trial Locations

Locations (24)

Peking University Third Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Chest Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

The Affilated Hospital of Inner Mongolia Medical University; 🇨🇳 Hohhot, Neimenggu, China

Cancer Hospital Chinese Academy Of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Pecking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

Harbin Medical University Cancer Hospital-Mammary gland of internal; 🇨🇳 Ha'erbin, Heilongjiang, China

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

The Second Hospital of Dalian Medical University; 🇨🇳 Dalian, Liaoning, China

Qilu Hospital of Shandong University; 🇨🇳 Jinan, Shandong, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

Renmin Hospital Of Wuhan University; 🇨🇳 Wuhan, Hubei, China

Xiangya Hospital Central South Univesity; 🇨🇳 Changsha, Hunan, China

Liaoning Cancer Hospital & Institute; 🇨🇳 Shenyang, Liaoning, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

Shandong Cancer Hospital; 🇨🇳 Jinan, Shandong, China

West China Hospital Sichuan University; 🇨🇳 Chendu, Sichuan, China

Fujian cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

Cancer Hospital Chinese Academy Of medical Sciences Shenzhen Center; 🇨🇳 Shenzhen, Guangdong, China

Beijing Tiantan Hospital, Captal Medical University; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Xi'An Jiaotong University; 🇨🇳 Xi'an, Shanxi, China

Tongji Hospital Tongji Medical College of Hust; 🇨🇳 Wuhan, Hubei, China

The First Hospital Of China Medical University; 🇨🇳 Shenyang, Liaoning, China

Union Hospital Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China