Interim Results of Phase 1/2 Trial of 4th-Gen EGFR-TKI 'JIN-A02' in NSCLC: Potential Breakthrough Against Acquired Therapy Resistance

J INTS BIO, a leading biopharmaceutical company based in Seoul, South Korea, has recently announced encouraging interim results from its Phase 1/2 clinical trial of JIN-A02, a pioneering fourth-generation EGFR Tyrosine Kinase Inhibitor (TKI). This novel treatment targets patients with non-small cell lung cancer (NSCLC) who have developed resistance to existing therapies and are experiencing disease progression. The findings were unveiled at the ENA Symposium held in Barcelona, Spain, from October 23-25, 2024, attracting significant interest from the global oncology community.

Mutations in the epidermal growth factor receptor (EGFR) play a critical role in the development of NSCLC, with third-generation EGFR-TKIs such as osimertinib being the primary treatment option. However, resistance to these treatments often develops, leading to cancer relapse and disease progression. JIN-A02, developed by J INTS BIO, is specifically designed to tackle both primary and acquired mutations, offering a new therapeutic solution for patients who no longer respond to third-generation EGFR-TKIs.

The Phase 1/2 clinical trial of JIN-A02 aims to evaluate its effectiveness in patients with advanced or metastatic NSCLC who have become resistant to third-generation EGFR-TKIs. The trial is divided into three parts: dose escalation (Part A), dose exploration (Part B), and dose expansion (Part C). The interim results from Part A have shown a promising safety profile and early efficacy signals, positioning JIN-A02 as a potential new treatment for EGFR-TKI-resistant NSCLC.

In Part A of the study, 16 patients received escalating doses of JIN-A02, ranging from 12.5mg to 150mg daily. The primary goal was to determine the maximum tolerated dose (MTD), while secondary objectives included assessing safety, pharmacokinetics, and anti-tumor activity. Higher doses than 150mg are currently being tested.

The key interim findings are as follows:

1. Safety: JIN-A02 demonstrated excellent tolerability at all dose levels studied so far, with no dose-limiting toxicities (DLTs) observed up to 150mg daily. Importantly, no adverse events commonly associated with EGFR TKIs, such as rash, diarrhea, and cardiotoxicity, were reported, despite reductions in tumor size. This positive safety profile has led to the exploration of higher doses.

2. Efficacy: Early tumor control was observed at lower doses, with the first instance occurring at a relatively low dose of 50mg. In this cohort, a partial response of lung lesions along with stable disease in brain metastases was reported. Another partial response of lung lesions was noted in the next cohort of 100mg, in a patient with a similar primary EGFR mutation. These results highlight the potential of JIN-A02 as an effective therapy for patients with progressive diseases who have previously received multiple treatments.

3. Central Nervous System (CNS): JIN-A02 has shown activity against brain metastases, a serious complication of progressive lung disease. Tumor reduction in brain metastases was first observed in the 100mg cohort, while stable disease was reported in the 50mg cohort. These findings indicate that JIN-A02 can penetrate the blood-brain barrier and exert anti-tumor effects in the CNS.

As the study progresses to subsequent phases, Part B will involve dose-expansion, where two selected doses will be studied in larger groups to verify safety, pharmacokinetics, and anti-tumor activity. This phase is crucial for determining the final dose to be used in Phase 2 or Part C. In Part C, JIN-A02 will be investigated in specific patient populations, stratified by EGFR mutation subtypes and the presence of CNS metastases. This phase is vital for generating a more comprehensive dataset on the drug's therapeutic potential across various NSCLC patient groups, aiming for regulatory approval.

Professor Byeong Cheol Cho from Severance Hospital's Division of Medical Oncology in South Korea emphasized the significance of these findings, noting that JIN-A02's efficacy against both lung cancer and CNS disease highlights its potential as a groundbreaking treatment for patients with EGFR-TKI-resistant NSCLC, especially those with brain metastases.

J INTS BIO remains dedicated to advancing the clinical development of JIN-A02. As patient enrollment continues ahead of schedule, JIN-A02 is set to transform the treatment landscape for NSCLC, offering new hope to lung cancer patients worldwide.