Iruplinalkib Showed Favorable Activity Against G1202R Resistance Mutation in NSCLC

By: JNCCN 360 Staff
Posted: Friday, July 11, 2025

Iruplinalkib, a novel and highly selective anaplastic lymphoma kinase (ALK) inhibitor, has shown strong activity and manageable safety profiles in patients with ALK-rearranged non–small cell lung cancer (NSCLC). However, evidence of the drug for uncommon ALK double fusion and secondary G1202R resistance mutation has been limited.

A case study reported by Guangjian Yang, Jiaqi Hu, and colleagues in Anti-Cancer Drugs was performed on a 36-year-old male patient with metastatic NSCLC harboring uncommon TTC7A-ALK and EML4-ALK double fusion. The patient had been given alectinib as first-line therapy and achieved a progression-free survival (PFS) of 20 months. Upon disease progression, iruplinalkib was prescribed as second-line therapy (180 mg once daily, with a 7-day lead-in phase at 60 mg once daily).

A 2-month follow-up showed that the patient had responded with a sustained decrease on the metastatic paraesophageal lymph node, while other metastases remained stable. An ongoing PFS benefit of 10 months was reported, with only mild (grade 1) adverse events (hypercholesterolemia and hypertriglyceridemia).

Cell-line models for iruplinalkib have shown that the drug has superior inhibitory activity against resistance mutations, including G1202R. It has also displayed strong inhibitory activity against mutations such as C1156Y, I1171N/S/T, F1174C/L/V, L1196M, and G1269A, suggesting its potential as a potent therapeutic agent for patients with ALK resistance mutations.

According to the authors, “This is the first case demonstrating favorable activity of iruplinalkib for G1202R resistance mutation in a NSCLC patient with uncommon TTC7A-ALK and EML4-ALK double fusion.”

Disclosure: The authors reported no conflicts of interest. For full disclosures of the study authors, visit journals.lww.com.

Anti-Cancer Drugs

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