What is the therapeutic effect of Mobotinib/Mobotinib?

Mobocertinib/Mobocertinib is an oral TKI that targets EGFR exon 20 insertion mutations in non-small cell lung cancer and has demonstrated promising results in Phase 1 and 2 clinical trials that evaluated patients who had previously received systemic therapy for locally advanced or metastatic disease. The efficacy of mobosetinib inEGFRex20ins-positive non-small cell lung cancer comes from the C5-carboxylate isopropyl ester moiety on its middle pyrimidine ring, which interacts with the C790 gatekeeper residue in the ATP-binding pocket of mutant EGFR.

The safety of moboxetinib was studied ina phase 1/2 trial. During the dose escalation phase, no dose-limiting toxicities (DLTs) occurred at doses between 5 and 40 mg/day. The overall response rate (ORR) of mobosetinib was 43% (12/28; 95% confidence interval [CI]: 24-63%), and the median duration of response (mDO R) was 13.9 months (95% CI: 5.0-not reached) and mPFS was 7.3 months (95% CI: 4.4-15.6). Additionally, the investigator-confirmed ORR was 56% (9/16; 95% CI: 30-80%) and 25% (3/12; 95% CI: 5-57%) in patients without and with baseline brain metastases, respectively. Similarly, mDOR was assessed at 13.8 months (95% CI: 5.0-16.6) and 5.5 months (95% CI: 3.0-1.42) in confirmed responders without and with baseline brain metastases, respectively. Investigator-assessed mPFS was 10.2 months (95% CI: 5.6-not reached) for patients without baseline brain metastases and 3.7 months (95% CI: 1.8-15.9) for patients with baseline brain metastases. Therefore, moboxetinib exhibits limited intracranial activity.

Given the ORR and long-term benefits observed in initial clinical trials, multiple countries around the world have approved Breakthrough Therapy Designation for mobosertinib for the treatment of patients with locally advanced or metastatic non-small cell lung cancer harboring EGFRex20ins mutations who have progressed despite treatment with platinum-based chemotherapy.

References:https://www.dovepress.com/clinical-utility-of-mobocertinib-in-the-treatment-of-nsclc--patient-se-peer-reviewed-fulltext-article-OTT