A Phase I/IIa Study of JAB-23E73 in Patients With Advanced Solid Tumors Harboring KRAS Gene Alteration

A Multicenter, Open Phase I/IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of JAB-23E73 in Patients With Advanced Solid Tumors Harboring KRAS Gene Alteration

This is a multicenter, open-label, phase I/IIa to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of pan-KRAS inhibitor JAB-23E73 in patients with advanced solid tumors harboring KRAS mutations or amplification. The study consists of 2 phases: Phase 1 Dose Escalation and Phase IIa Dose Expansion.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: JAB-23E73

Detailed Description

Study JAB-23E73-1001 is a global multicenter, open-label Phase 1/2a study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anticancer activity of JAB-23E73 as a single agent in adult patients with advanced solid tumors with KRAS alteration. This study consists of a Phase 1a dose-escalation, followed by Phase 1b dose-expansion (dose optimization) and Phase 2a indication expansion. After completing dose-escalation, the MTD or preliminary RP2D of JAB-23E73 will be determined. Then, two of the alternative dosages of JAB-23E73 will be selected to further evaluate the efficacy, safety and PK in patients with KRAS-alternated NSCLC or other tumors, and patients may be further selected by certain/several types of KRAS-alternations based on dose escalation data. The RP2D will be determined according to the safety, efficacy and PK data from phase 1b.

• Study Type: Interventional
• Enrollment (Estimated): 334
• 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
  • Anhui
    • Hefei, Anhui, China, 230001
      • Not yet recruiting
      • Anhui Provincial Cancer Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Recruiting
      • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Beijing, Beijing Municipality, China, 100050
      • Not yet recruiting
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China, 100032
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100032
      • Recruiting
      • Beijing Chest Hospital
    • Beijing, Beijing Municipality, China, 100032
      • Recruiting
      • Peking Union Medical College Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Not yet recruiting
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Guangxi
    • Nanning, Guangxi, China, 530012
      • Recruiting
      • Guangxi Medical University Cancer Hospital
  • Hebei
    • Langfang, Hebei, China, 065000
      • Recruiting
      • National Cancer Center/Cancer Hospital- Langfang Campus, Chinese Academy of Medical Sciences and Peking Union Medical College
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150081
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The first affiliated hospital of Zhengzhou university
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Recruiting
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430030
      • Not yet recruiting
      • Tongji Hospital
  • Hunan
    • Changsha, Hunan, China, 200032
      • Not yet recruiting
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China, 210009
      • Not yet recruiting
      • Jiangsu Cancer Hospital
    • Suzhou, Jiangsu, China, 215006
      • Not yet recruiting
      • The First Affiliate of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of NanChang University
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Recruiting
      • The First Hospital of China Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200040
      • Not yet recruiting
      • Huashan Hospital Fudan University
    • Shanghai, Shanghai Municipality, China, 200025
      • Not yet recruiting
      • Shanghai Jiaotong University School of Medicine Ruijin Hospital
    • Shanghai, Shanghai Municipality, China, 200032
      • Not yet recruiting
      • Fudan University Zhongshan Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 650118
      • Recruiting
      • Shanxi Cancer Hospital
    • Xi’an, Shanxi, China, 710061
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Not yet recruiting
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300211
      • Not yet recruiting
      • Tianjin Medical University Cancer Institute&Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Recruiting
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310014
      • Not yet recruiting
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China, 310009
      • Not yet recruiting
      • The Second Affiliate Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer with evidence of KRAS gene alteration (including gene mutation and wild type amplification).
2. Able to provide an archived tumor tissue sample or fresh biopsy sample.
3. Life expectancy ≥3 months at the start of treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. ≥1 measurable lesion per RECIST v1.1.
6. Adequate organ function.

Exclusion Criteria:

1. Unable to swallow oral medications or with gastrointestinal dysfunction or gastrointestinal disease that significantly alters the absorption of medication.
2. Previous treatment with rat sarcoma (RAS) targeting agents.
3. Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
4. Impaired cardiovascular function or clinically significant cardiac disease.
5. Mean QT interval corrected using Fridericia's formula (QTcF) >470 msec.
6. Females who are pregnant or breastfeeding.

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: Phase 1 Dose Exploration; Monotherapy, dose escalation	Drug: JAB-23E73; Administered orally
Experimental: Phase 2a Dose Expansion; Monotherapy, dose expansion	Drug: JAB-23E73; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of participants with dose limiting toxicities (DLT)	Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. DLTs will be defined as the occurrence of any of the toxicities as described in the protocol.	Up to 21 days
Phase 2a: Objective response rate (ORR)	ORR is defined as the proportion of patients with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2a: Pharmacokinetic (PK): Maximum concentration (Cmax) of JAB-23E73	PK: Cmax of JAB-23E73	Up to approximately 2 years
Phase 1/2a: PK: Time to Maximum Concentration (Tmax) of JAB-23E73	PK: Tmax of JAB-23E73	Up to approximately 2 years
Phase 1/2a: PK: Area Under the Concentration Versus Time Curve (AUC) of JAB-23E73	PK: AUC of JAB-23E73	Up to approximately 2 years
Phase 1: ORR	ORR is defined as the proportion of patients with a BOR of confirmed CR or confirmed PR per RECIST v1.1.	Up to approximately 2 years
Phase 1/2a: Time to Response (TTR)	TTR is defined as the time from the date of first dose of study drug to first documentation of response as assessed by the investigator per RECIST v1.1	Up to approximately 2 years
Phase 1/2a: Progression Free Survival (PFS)	PFS is defined as the time from the date of the first dose of study drug to the date of the first documentation of progressive disease assessed by the investigator per RECIST v1.1 or death, whichever occurs first.	Up to approximately 2 years
Phase 1/2a: Disease Control Rate (DCR)	DCR is defined as the proportion of patients with CR, PR, or stable disease (SD) as assessed by the investigator per RECIST v1.1	Up to approximately 2 years
Phase 1/2a: Duration of Response (DoR)	DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.	Up to approximately 2 years
Phase 2a: Overall Survival (OS)	OS is defined as the time from the date of first dose of study drug until the date of death from any cause.	Up to approximately 2 years
Phase 1/2a: Adverse events	Incidence and severity of treatment-emergent Adverse Events (TEAEs), treatment-related Adverse Events (TRAEs) and serious Adverse Events (SAEs)	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: April 28, 2025
• First Submitted That Met QC Criteria: April 28, 2025
• First Posted (Actual): May 6, 2025

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Colorectal cancer; KRAS mutation; KRAS; Pancreas cancer; Targeted Therapy; KRAS-mutant tumor; KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12S, KRAS G12A, KRAS G12D; Pan-KRAS; JAB-23E73
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Colonic Diseases; Colorectal Neoplasms; Pancreatic Neoplasms
• Other Study ID Numbers: JAB-23E73-1001

Drug and device information, study documents

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