How long does it usually take to become resistant to mobosetinib/mobosetinib?

Mobocertinib/Mobocertinib is a targeted therapy drug targeting EGFR (epidermal growth factor receptor) mutations. It is mainly used to treat non-small cell lung cancer (NSCLC) with specific EGFR mutations. Although it has achieved remarkable results in clinical treatment, drug resistance remains a major challenge in cancer treatment.

The oral epidermal growth factor receptor (EGFR) inhibitor moboxetinib was evaluated in a phase 1/2 dose escalation/expansion trial for EGFR gene mutations including exon 20 insertions (EGFRex20ins) in non-small cell lung cancer. Dose escalation determined 160 mg daily as the recommended Phase 2 dose and maximum tolerated dose. Among 28 patients receiving EGFRex20ins 160 mg daily, investigator-assessed confirmed response rate was 43% (12/28; 95% confidence interval [CI]: 24-63%), with median response duration The median progression-free survival was 14 months (5.0-not reached) , and the median progression-free survival was 7.3 months (4.4-15.6) . Mobosetinib showed antitumor activity in patients with different EGFRex20ins variants, with a safety profile consistent with other EGFR inhibitors.

Regarding resistance to mobosetinib, studies have found that patients usually develop resistance within a few months to a year after receiving the drug. The exact length of time varies based on individual differences, the biology of the tumor, and the patient's overall health. Generally speaking, most patients will develop disease progression or tumor resistance to the drug within 6 to 12 months after taking moboxetinib.

The development of drug resistance mechanisms is often related to genetic mutations in tumor cells. EGFR-mutated tumor cells may develop drug resistance through multiple pathways after being exposed to mobosetinib. For example, some patients may develop new EGFR mutations, such as the T790M mutation, which can lead to reduced drug binding to the target. In addition, tumor cells may also evade the inhibitory effects of drugs by activating other signaling pathways (such as the MET or HER2 pathways).