KRAS specific therapy

CompoundJAB-23E73

Area under investigation

Advanced Solid Tumors, Pancreatic cancer

Scientific PillarCell Therapy

 

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NCT06973564 trial overview

Tumor

Advanced solid tumors with KRAS alterations, including CRC, PDAC, NSCLC and other solid tumors

Trial Identifier

NCT06973564

Phase

I/IIa

Regimen

JAB-23E73 monotherapy and chemotherapy combinations

Partnered (Jacobio)

Target Overview

KRAS is a small GTPase that functions as a molecular switch, cycling between GDP-bound and GTP-bound states to regulate downstream effector pathways controlling cellular proliferation and survival1.

KRAS is a major oncogenic driver and the most frequently mutated member of the RAS family in human cancers. Mutations in KRAS are particularly prevalent in pancreatic, colorectal and lung cancers, making it an important therapeutic target2.

A pan-KRAS inhibitor capable of targeting multiple oncogenic KRAS mutant variants could address a broad range of KRAS-driven tumours. Selectivity for KRAS over NRAS and HRAS may enhance the therapeutic window, support broader combination treatment strategies and expand the number of patients who could benefit from therapy3.

Compound Overview

JAB-23E73 is an allosteric pan-KRAS inhibitor designed to target both the GDP-bound “OFF” state and the GTP-bound “ON” state of KRAS. The compound inhibits multiple oncogenic KRAS mutations as well as wild type KRAS, while maintaining selectivity over NRAS and HRAS.4 It is currently being investigated as a potential treatment for KRAS-driven cancers.

Mechanism of Action

  • Mechanism of Action

References

 

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NCT06973564 trial overview

Tumor

Advanced solid tumors with KRAS alterations, including CRC, PDAC, NSCLC and other solid tumors

Trial Identifier

NCT06973564

Phase

I/IIa

Regimen

JAB-23E73 monotherapy and chemotherapy combinations

Partnered (Jacobio)

Abbreviations

  • AEs

    Adverse events

  • AUC

    Area under the curve

  • Cmax

    Maximum plasma concentration

  • CTCAE

    Common Terminology Criteria for Adverse Events

  • Ctrough

    Trough plasma concentration

  • CRC

    Colorectal cancer

  • DCR

    Disease control rate

  • DLT

    Dose-limiting toxicity

  • DOR

    Duration of response

  • ECOG PS

    Eastern Cooperative Oncology Group performance status

  • KRAS

    Kirsten rat sarcoma viral oncogene homolog

  • nab

    Nanoparticle albumin-bound

  • NCT

    National Clinical Trial

  • NSCLC

    Non-small cell lung cancer

  • ORR

    Objective response rate

  • OS

    Overall survival

  • PDAC

    Pancreatic ductal adenocarcinoma

  • PFS

    Progression-free survival

  • PK

    Pharmacokinetics

  • RP3D

    Recommended Phase 3 dose

  • TTR

    Time to response