EGFR Exon20+ NSCLC: Trial Data With Mobocertinib

EP: 1.Paradigm of NGS Testing in Patients With Advanced NSCLC

EP: 2.Uncommon EGFR Mutations in Advanced Non–Small Cell Lung Cancer

EP: 3.First- and Second-Line Treatment Options for EGFR Exon20+ NSCLC

EP: 4.Trial Data and Experience With Amivantamab in EGFR Exon20+ NSCLC

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EP: 5.EGFR Exon20+ NSCLC: Trial Data With Mobocertinib

EP: 6.Factors in Selecting Novel Therapy for Patients With EGFR Exon20+ NSCLC

EP: 7.Advanced NSCLC: CNS Penetration With Novel EGFR TKI Therapy

EP: 8.Evolving Management of EGFR Exon20+ NSCLC: Future Directions in Care

EP: 9.Amivantamab vs Mobocertinib in Exon 20 NSCLC

EP: 10.Frontline Forum: Testing and Targeted Therapy in EGFR Exon20+ NSCLC

Transcript:

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.