Background: Mobocertinib is a potent, irreversible, oral tyrosine kinase inhibitor selectively targeting EGFR ex20ins in NSCLC. Mobocertinib demonstrated clinical efficacy in 114 platinum-pretreated pts (PPP) with EGFR ex20ins+ mNSCLC in a phase 1/2 study. Methods: In this study (NCT02716116), pts with ECOG status 0–1 and ≥1 prior therapy line for locally advanced/metastatic EGFR ex20ins+ NSCLC received mobocertinib 160 mg QD. Pts were allowed to continue tx beyond PD at the discretion of the investigator (INV) if evidence of clinical benefit existed. We present data on continuation of mobocertinib tx beyond PD in the PPP cohort by site of first PD (brain vs extracranial). Results: At the November 1, 2020, data cutoff, among PPP (n=114; median age 60 y, 66% female, 60% Asian), 59% had ≥2 prior systemic anticancer lines; 35% had baseline brain metastases (Zhou C, et al. JAMA Oncol. 2021;7(12):e214761. doi:10.1001/jamaoncol.2021). Confirmed objective response rate (cORR) per independent review committee (IRC) was 28%; median duration of response was 17.5 mo. IRC-assessed cORR was 34% among PPP with no baseline brain metastases versus 18% among PPP with baseline brain metastases (Zhou C, et al. JAMA Oncol. 2021;7(12):e214761. doi:10.1001/jamaoncol.2021); median progression-free survival was 9.2 and 3.7 mo, respectively. Per INV assessment, 64 pts had PD. Duration of mobocertinib tx beyond PD is summarized in the Table. Among pts with first site of PD in brain per INV (n=21), 17 (81%) pts remained on mobocertinib tx beyond PD; 7 (33%) received radiotherapy to brain and remained on mobocertinib tx, of whom 3 pts remained on mobocertinib tx for ≥6 mo and 1 pt for ≥12 mo. Among pts with first site of PD outside the brain per INV (n=43), 28 (65%) pts continued tx beyond PD and 4 (9%) pts remained on mobocertinib tx for ≥6 mo. Conclusions: These results suggest that mobocertinib may have limited intracranial activity given the high frequency of first PD in brain (25%) and numerically lower IRC-assessed cORR in pts with baseline brain metastases. Per INV assessment, pts may derive ongoing systemic benefit from mobocertinib. Duration of time to next progression based on local therapy continues to be investigated. Clinical trial information: NCT02716116.

INV, investigator; PD, progressive disease.