Joshua Sabari, MD, and Misako Nagasaka, MD, reflect on clinical trial data and experience with mobocertinib in patients with EGFR Exon20+ non–small cell lung cancer.
Joshua K. Sabari, MD: Dr Nagasaka, there’s another agent, mobocertinib, an EGFR and HER2 exon 20 TKI [tyrosine kinase inhibitor]. Walk us through those data.
Misako Nagasaka, MD: Yes. So mobocertinib, or mobo for short, is a potent oral small-molecule tyrosine kinase inhibitor that targets EGFR exon 20 insertion mutations. And mobo is structurally designed to gain selectivity by targeting proteins in the vicinity of the αC helix, a binding site not exploited by osimertinib. So the study that led to the approval of mobo was called EXCLAIM study [NCT04129502]. And it had several cohorts. The most important cohort perhaps is the PPP cohort, which is [the] platinum-pretreated patient cohort. And in that, they included 114 patients with EGFR exon 20 insertion mutations. And they received mobocertinib at 160 mg once daily. There was also the exclaimed cohort, which basically included 96 patients who were previously treated [and had] EGFR exon 20 insertion–mutated non–small cell lung cancer. And initially, they presented their investigator-assessed objective response rate, which was 35% in the PPP [cohort] and 32% in the EXCLAIM cohort. So previously treated patients. But then the…blinded investigator-reviewed committee [IRC]–assessed objective response rate was 28% for the PPP. Although the response rate was in the range of 28% to 35%, what the study [results] showed was an impressive waterfall plot with 84% of patients having a reduction from baseline in some of target lesion diameters per IRC assessments. The other [piece of] impressive data was the duration of response, which was about 17.5 months. But then the toxicity was an issue. So compared with amivantamab, where the toxicity was mainly the infusion-related reaction that you see for cycle 1, day 1, mobocertinib had more EGFR-related toxicities. And the major one was diarrhea. So any-grade diarrhea was 91%, and grade 3 or higher diarrhea was 21%.
Transcript edited for clarity.