Multinational phase 3 trial of first-line mobocertinib versus chemotherapy for EGFR ex20ins+ metastatic non-small cell lung cancer

Mobocertinib is an EGFR TKI that targets EGFR exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). The multinational phase 3 EXCLAIM-2 trial compared mobocertinib versus platinum-based chemotherapy as first-line treatment for EGFR ex20ins+ locally advanced or metastatic NSCLC. Primary endpoint was progression-free survival by blinded independent central review (PFS per BICR). At the first interim analysis, the median PFS per BICR was 9.6 months in both arms. Confirmed objective response rate per BICR was 32% with mobocertinib versus 30% with chemotherapy, with median duration of response 12.0 versus 8.4 months. There were clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. The authors conclude that EXCLAIM-2 did not meet its primary endpoint. The efficacy of mobocertinib was not superior to platinum-based chemotherapy in first-line treatment of patients with EGFR ex20ins+ locally advanced or metastatic NSCLC.