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KRAS specific therapy

CompoundJAB-23E73

Area under investigation

Advanced Solid Tumors, Pancreatic cancer

Scientific PillarCell Therapy

 

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NCT07640295 trial overview

Tumor

Treatment-naïve metastatic PDAC harboring KRAS gene alterations

Trial Identifier

NCT07640295

Phase

Ib/III

Regimen

JAB-23E73 + nab-paclitaxel + gemcitabine

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Partnered (Jacobio) China only

Study Design

Inclusion criteria

 

The key inclusion criteria are –

  • Histologically or cytologically confirmed metastatic PDAC
  • No prior systemic antitumor therapy for advanced disease (treatment-naive)
  • Presence of KRAS gene alterations be enrolled upon approval by the sponsor
  • ECOG PS score of 0 or 1
  • Adequate organ function

 

Reference:

Study NCT07640295. ClinicalTrials.gov website.

 

Exclusion criteria

 

The key exclusion criteria are –

  • Inability to swallow oral medications or the presence of  GI dysfunction or disease that may significantly alter drug absorption.
  • 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.
  • Prior treatment with KRAS G12C inhibitors, KRAS G12D inhibitors, pan-KRAS/pan RAS inhibitors, or other agents of the same class.
  • Women who are pregnant or breast-feeding.
  • Patients who have progressive disease or recurrence during neoadjuvant or adjuvant treatment, or within 6 months after the last dose of medication.

NCT07640295 Overview Modal

NCT07640295 trial overview

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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

1. Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170:17–33. 2.Prior IA , Hood FE , Hartley JL . The frequency of Ras mutations in cancer. Cancer Res 2020;80:2969–74. 3. Riedl JM et al. Emerging landscape of KRAS inhibitors in cancer treatment. Cancer Cell 2026; 44, 471-497 4. Wang P et al. Preclinical investigation of orally bioavailable, potent pan-KRAS (ON/OFF) inhibitor JAB-23E73 [abstract] In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A068.

 

Loading......

NCT07640295 trial overview

Tumor

Treatment-naïve metastatic PDAC harboring KRAS gene alterations

Trial Identifier

NCT07640295

Phase

Ib/III

Regimen

JAB-23E73 + nab-paclitaxel + gemcitabine

Visit ct.gov

Partnered (Jacobio) China only

Study Design

Inclusion criteria

 

The key inclusion criteria are –

  • Histologically or cytologically confirmed metastatic PDAC
  • No prior systemic antitumor therapy for advanced disease (treatment-naive)
  • Presence of KRAS gene alterations be enrolled upon approval by the sponsor
  • ECOG PS score of 0 or 1
  • Adequate organ function

 

Reference:

Study NCT07640295. ClinicalTrials.gov website.

 

Exclusion criteria

 

The key exclusion criteria are –

  • Inability to swallow oral medications or the presence of  GI dysfunction or disease that may significantly alter drug absorption.
  • 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.
  • Prior treatment with KRAS G12C inhibitors, KRAS G12D inhibitors, pan-KRAS/pan RAS inhibitors, or other agents of the same class.
  • Women who are pregnant or breast-feeding.
  • Patients who have progressive disease or recurrence during neoadjuvant or adjuvant treatment, or within 6 months after the last dose of medication.

NCT07640295 Overview Modal

NCT07640295 trial overview

Take me to ClinicalTrials.Gov

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

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Abbreviations

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  • 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

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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