JIN-A02 Overcomes Tagrisso Resistance via C797S and T790M Targeting

Research published by J INTS BIO in the journal Clinical Cancer Research introduces JIN-A02, an investigational fourth-generation tyrosine kinase inhibitor (TKI) designed specifically to overcome the C797S mutation, a significant resistance mutation that has been commonly found following third-generation treatments for non-small cell lung cancer (NSCLC).¹ The advancement of the epidermal growth factor receptor (EGFR) therapies has significantly altered the NSCLC treatment landscape.

How Does this New Molecule Address the Limitations of Third-Generation Inhibitors?

The development of JIN-A02 reflects a shift toward high-selectivity drug design.¹ It is engineered as an orally available TKI that targets both C797S and T790M mutations while maintaining minimal activity against wild-type EGFR. This selectivity is vital for teams aiming to maximize therapeutic indices and minimize off-target effects. In preclinical studies, the molecule demonstrated tumor regression in models of NSCLC that were resistant to third-generation standards, achieving a tumor growth inhibition of 168.2%. Beyond simple growth suppression, tumor tissue analyses revealed molecular-level efficacy through significant reductions in phosphorylated EGFR and the proliferation marker Ki-67.

What Do Initial Clinical and Preclinical Indicators Suggest About its Therapeutic Viability?

JIN-A02 has shown the ability to achieve therapeutically relevant exposure across the blood–brain barrier.¹ In intracranial models, the treatment produced rapid and sustained reductions in tumor burden. These preclinical signals are reinforced by early observations from an ongoing Phase 1/2 trial involving patients with NSCLC who progressed after prior EGFR-targeted therapies. In one clinical case, a 300 mg dose resulted in a 44.9% reduction in lung lesions and a 25% reduction in brain metastatic lesions by the seventh treatment cycle.

The clinical utility of JIN-A02 is further supported using circulating tumor DNA (ctDNA) as a biomarker for molecular response.¹ Analysis of a patient’s ctDNA showed a complete clearance of the EGFR C797S mutation and more than a 90% reduction in the T790M mutation. Commenting on these results in a press release, Prof. Sun Min Lim of the Division of Medical Oncology at Severance Hospital noted, "JIN-A02 has demonstrated meaningful preclinical activity and early clinical signals targeting C797S-mediated resistance, for which treatment options have been extremely limited following the failure of third-generation EGFR-targeted therapies. In particular, the observed activity in brain metastases, along with a reduction in EGFR mutations detected in plasma ctDNA, provides important support for its further clinical development.”¹

How Else Is Lung Cancer Research Developing?

While molecularly targeted therapies advance for NSCLC, the treatment paradigm for extensive-stage small cell lung cancer (ES-SCLC) is also evolving through newly approved combination maintenance strategies.² In late 2025, regulatory approval was granted for lurbinectedin in combination with atezolizumab for patients whose disease did not progress after initial induction therapy.

The combination of lurbinectedin and atezolizumab demonstrated a median overall survival (OS) of 13.2 months, compared to 10.6 months for atezolizumab monotherapy.² Furthermore, the median progression-free survival (PFS) reached 5.4 months with the combination versus 2.1 months in the control arm. These results underscore the value of validating the synergistic potential of cytotoxic agents with immunotherapy. Manufacturing and safety teams must remain focused on managing combined risk profiles, which include warnings for myelosuppression and immune-mediated adverse reactions.

What Are the Regulatory Implications for Pursuing Global Oncology Approvals?

The approval of this therapy was facilitated through Project Orbis, an initiative allowing concurrent review among international regulatory partners.² This framework, combined with priority review, highlights the accelerating pathway for therapies addressing serious conditions. The success of this maintenance strategy provides a clear template for leveraging multi-agent protocols to improve OS and PFS populations that are difficult to treat.

References

1. J INTS BIO. J INTS BIO Reports Fourth-Generation EGFR Inhibitor JIN-A02 in Clinical Cancer Research. Press Release. Feb 12, 2026.
2. FDA. FDA Approves Lurbinectedin in Combination with Atezolizumab or Atezolizumab And Hyaluronidase-Tqjs for Extensive-Stage Small Cell Lung Cancer. Press Release. Oct 2, 2025.