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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Non-small Cell Lung Cancer; Pancreatic Ductal Carcinoma; KRAS P.G12C
• Intervention / Treatment: Drug: JAB-21822; Drug: JAB-3312

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100191
      • Recruiting
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100005
      • Not yet recruiting
      • Pecking Union Medical College Hospital
    • Beijing, Beijing, China, 100070
      • Not yet recruiting
      • Beijing Tiantan Hospital, Captal Medical University
    • Beijing, Beijing, China, 101125
      • Not yet recruiting
      • Beijing Chest Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Not yet recruiting
      • Fujian cancer hospital
  • Guangdong
    • Shenzhen, Guangdong, China, 518116
      • Not yet recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Center
  • Heilongjiang
    • Ha'erbin, Heilongjiang, China, 150081
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital-Mammary gland of internal
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Not yet recruiting
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Not yet recruiting
      • Renmin Hospital of Wuhan University
    • Wuhan, Hubei, China, 430022
      • Not yet recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Not yet recruiting
      • Tongji Hospital Tongji Medical College of HUST
  • Hunan
    • Changsha, Hunan, China, 410008
      • Not yet recruiting
      • Xiangya Hospital Central South Univesity
    • Changsha, Hunan, China, 410031
      • Not yet recruiting
      • Hunan Cancer Hospital
  • Liaoning
    • Dalian, Liaoning, China, 116023
      • Not yet recruiting
      • The Second Hospital of Dalian Medical University
    • Shenyang, Liaoning, China, 110001
      • Not yet recruiting
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110801
      • Not yet recruiting
      • Liaoning cancer Hospital & Institute
  • Neimenggu
    • Hohhot, Neimenggu, China, 750306
      • Not yet recruiting
      • The Affilated Hospital of Inner Mongolia Medical University
  • Shandong
    • Jinan, Shandong, China, 250012
      • Not yet recruiting
      • Qilu Hospital Of Shandong University
    • Jinan, Shandong, China, 250117
      • Not yet recruiting
      • Shandong Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Not yet recruiting
      • Fudan University Shanghai Cancer Center
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'An JiaoTong University
  • Sichuan
    • Chendu, Sichuan, China, 610044
      • Not yet recruiting
      • West China Hospital Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: March 11, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal
• Other Study ID Numbers: JAB-21822-1006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No