J INTS BIO presented encouraging interim results from its Phase 1/2 clinical trial of JIN-A02, a novel 4th-generation EGFR tyrosine kinase inhibitor (TKI), at the ENA (EORTC-NCI-AACR) Symposium in Barcelona. The study focuses on patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have developed resistance and progressive disease despite prior treatments. The data suggests JIN-A02 could offer a new therapeutic avenue for these patients.
Addressing Resistance to 3rd-Generation EGFR-TKIs
Mutations in the epidermal growth factor receptor (EGFR) are key drivers in NSCLC. Third-generation EGFR-TKIs, such as osimertinib, are standard treatments. However, resistance inevitably develops, leading to disease progression. JIN-A02 is designed to overcome this resistance by targeting both original and acquired mutations.
The ongoing Phase 1/2 trial includes dose escalation (Part A), dose exploration (Part B), and dose expansion (Part C). Part A data demonstrates a good safety profile and early efficacy signals, positioning JIN-A02 as a potential treatment for EGFR-TKI-resistant NSCLC.
Interim Phase 1/2 Results
Part A of the study enrolled 16 patients, with JIN-A02 doses ranging from 12.5mg to 150mg daily. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included assessing safety, pharmacokinetics, and anti-tumor activity. Higher doses are currently under investigation.
Key interim findings include:
- Safety: JIN-A02 showed favorable tolerability across all dose levels, with no dose-limiting toxicities (DLTs) observed up to 150mg daily. There was no myelosuppression or adverse events commonly associated with EGFR TKIs, such as rash, diarrhea, or cardiotoxicity.
- Efficacy: Tumor control was reported early, even at a low dose of 50mg. One patient in this cohort experienced a partial response in lung lesions and stable disease in brain metastases. Another partial response in lung lesions was observed in the 100mg cohort in a patient with a similar primary EGFR mutation.
- Central Nervous System (CNS) Activity: JIN-A02 demonstrated activity against brain metastases. Reduction in brain metastases was reported in the 100mg cohort, while stable disease was reported in the 50mg cohort, suggesting the drug can penetrate the blood-brain barrier and exert anti-tumor effects.
Progression to Subsequent Trial Phases
Following determination of final doses, the dose-expansion part of the study (Part B) will commence, evaluating two doses in larger patient groups to confirm safety, pharmacokinetics, and anti-tumor activity. Part B will inform the selection of the final dose for Phase 2 (Part C).
Part C will investigate JIN-A02 in specific patient populations stratified by EGFR mutation subtypes and the presence of CNS metastases. This phase aims to generate a larger dataset on the drug's therapeutic potential across distinct NSCLC patient groups for regulatory approval.
Expert Commentary
Professor Byeong Cheol Cho of Severance Hospital's Division of Medical Oncology, South Korea, noted, "JIN-A02's demonstrated efficacy against both lung and its associated CNS disease underscores its potential as a groundbreaking treatment for patients with EGFR-TKI-resistant NSCLC, including and especially those with brain metastases."
Next Steps
J INTS BIO is committed to accelerating the clinical development of JIN-A02, with ongoing patient enrollment ahead of schedule. The company believes JIN-A02 has the potential to reshape the treatment landscape of NSCLC and offer hope to lung cancer patients worldwide.
