Study of JAB-23E73 in Combination With Chemotherapy in Participants With Metastatic PDAC Harboring KRAS Gene Alterations

A Multicenter, Phase Ib/III Study to Evaluate JAB-23E73 in Combination With Nab-Paclitaxel and Gemcitabine in Participants With Metastatic Pancreatic Ductal Adenocarcinoma Harboring KRAS Gene Alterations

The purpose of this study is to determine the safety and efficacy of pan KRAS inhibitor JAB-23E73 in combination with nab-paclitaxel and gemcitabine in participants with metastatic PDAC harboring KRAS gene alterations.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: JAB-23E73 tablet，nab-paclitaxel，gemcitabine

Detailed Description

This is a phase Ib/III, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antineoplastic activity of pan-KRAS inhibitor JAB-23E73 in combination with nab-paclitaxel and gemcitabine in treatment-naive participants with metastatic PDAC.

Phase Ib study：an open-label study, including dose escalation and backfill cohorts, with approximately 40-80 participants planned to be enrolled (including approximately 20-50 participants in the backfill cohort),Aiming to determine the recommended phase III dose [RP3D] within investigated patient population groups.

Phase III: Following confirmation of the efficacy and safety of JAB-23E73 in combination with the AG regimen in Phase Ib, a Phase III trial will be initiated to evaluate the efficacy and safety of JAB-23E73 plus AG versus AG alone for the treatment of metastatic PDAC.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jacobio Pharmaceuticals; Phone Number: 86 10 56315466; Email: clinicaltrials@jacobiopharma.com

Study Locations

• China
  • Beijing, China
    • Beijing Tsinghua Changgung Hospital
    • Contact: Beijing Tsinghua Changgung Hospital; Phone Number: 86+13366152815; Email: joelbmu@126.com
  • Changsha, China
    • Hunan Cancer Hospital
    • Contact: Hunan Cancer Hospital; Phone Number: 86+18673181133; Email: liuzhenyang@hnca.org.cn
  • Harbin, China
    • Harbin Medical University Cancer Hospital
    • Contact: Harbin Medical University Cancer Hospital; Phone Number: 86+13845120210; Email: yanqiaozhang@126.com
  • Nanjing, China
    • Jiangsu Province Hospital
    • Contact: Jiangsu Province Hospital; Phone Number: 86+13585172066; Email: Xiaofengch198019@126.com
  • Shanghai, China
    • Shanghai Jiaotong University School of Medicine Ruijin Hospital
    • Contact: Shanghai Jiaotong University School of Medicine Ruijin Hospita; Phone Number: 86+13901943778 86+; Email: shenby@shsmu.edu.cn
  • Taiyuan, China
    • Shanxi Cancer Hospital
    • Contact: ShanXi Cancer Hospital; Phone Number: 86+13811176181; Email: WXCAMS@126.com
  • Wuhan, China
    • Wuhan Union Hospital Of China
    • Contact: Wuhan Union Hospital Of China; Phone Number: 86+13720117761; Email: heshuiwu@hust.ed.cn
  • Wuhan, China
    • Zhongnan Hospital of Wuhan University
    • Contact: Zhongnan Hospital of Wuhan University; Phone Number: 86-13971235235 86+13971235235; Email: pjxp888@126.com
  • Wuhan, China
    • Hubei Province Hospital
    • Contact: Hubei Province Hospital; Phone Number: 86+15629019627; Email: 971070316@qq.com
  • Zhengzhou, China
    • Henan Cancer Hospital
    • Contact: Henan Cancer Hospital; Phone Number: 86+13937100233; Email: 2290773710@qq.com
  • Zhengzhou, China
    • The First Affiliated Hospital of Zhengzhou University
    • Contact: The First Affiliated hospital of Zhengzhou University; Phone Number: 86+13676932999; Email: yanruqin@163.com
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
      • Contact: Beijing Cancer Hospital; Phone Number: 86+13911219511; Email: doctorshenlin@sina.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Zhejiang Cancer Hospital
      • Contact: Zhejiang Cancer Hospital; Phone Number: 86+13858195803; Email: hzyingjieer@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1.Written informed consent signed by the participant or the participant's legally authorized representative must be obtained prior to performing any study-related procedures. 2. Histologically or cytologically confirmed metastatic PDAC.

3. No prior systemic antitumor therapy for advanced disease (treatment-naïve). 4. Presence of KRAS gene alterations: be enrolled upon approval by the sponsor).

5. ECOG performance status score of 0 or 1. 6. Adequate organ function.

Exclusion Criteria:

1. Inability to swallow oral medications or the presence of gastrointestinal dysfunction or disease that may significantly alter drug absorption.
2. A history of another malignancy within 2 years prior to the first dose, histologically distinct from the cancer under study, except for carcinoma in situ of the cervix, superficial non-invasive bladder cancer, or adequately treated stage I non-melanoma skin cancer.
3. Prior treatment with KRAS G12C inhibitors, KRAS G12D inhibitors, pan-KRAS inhibitors, or other agents of the same class.
4. Primary central nervous system (CNS) tumors.
5. Women who are pregnant or breast-feeding.
6. Participants who have progressive disease or recurrence during neoadjuvant or adjuvant treatment, or within 6 months after the last dose of medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation/backfill	Drug: JAB-23E73 tablet，nab-paclitaxel，gemcitabine; Orally, intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities (DLT)	The number and proportion of participants who experienced dose-limiting toxicities (DLT).	Up to 28 days
Adverse events.safety evaluation	The types, incidence, severity, and outcomes of adverse events and serious adverse events evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate, ORR is defined as the proportion of participants with confirmed complete response or partial response	Up to approximately 3 years
DOR	Duration of response, DOR is defined as the time from the first documented CR or PR to the first occurrence of disease progression or death from any cause, whichever occurs first	Up to approximately 3 years
TTR	Time to Response, TTR is defined as the time from the first dose of study treatment to the first documented CR or PR.	Up to approximately 3 years
PFS	Progression-Free Survival , PFS is defined as the time from the first dose of study treatment to the first documented disease progression or death from any cause, whichever occurs first.	Up to approximately 3 years
DCR	Disease Control Rate, DCR is defined as the proportion of participants whose best overall response is CR, PR, or SD..	Up to approximately 3 years
OS	Overall Survival , OS is defined as the time from the first dose of study treatment to death from any cause.	Up to approximately 3 years
PK	maximum plasma concentration (Cmax)	Up to approximately 3 years
PK	area under the plasma concentration-time curve (AUC)	Up to approximately 3 years
PK	trough plasma concentration (Ctrough)	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Jacobio Pharmaceuticals Co., Ltd.
• Investigators: Study Director: Jacobio Pharmaceuticals, Jacobio Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 22, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: KRAS mutation; Pancreatic ductal adenocarcinoma; KRAS; Targeted Therapy; KRAS-mutant tumor; Pan-KRAS; JAB-23E73; KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12S, KRAS G12A,
• Other Study ID Numbers: JAB-23E73-2001

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