Amivantamab plus chemotherapy vs. chemotherapy in participants with EGFR-mutant advanced non-small cell lung cancer after progression on osimertinib: a MARIPOSA-2 analysis of the Asian subgroup

Abstract

Background The Phase 3 MARIPOSA-2 study showed that amivantamab, a bispecific antibody with immune cell-directing activity, plus chemotherapy significantly improved progression-free survival (PFS) compared with chemotherapy alone in participants with common epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), whose disease had progressed on osimertinib monotherapy. We conducted a post hoc analysis to assess clinical outcomes in the Asian subgroup of participants from MARIPOSA-2 (NCT04988295). Methods Participants were randomised 2:2:1 to amivantamab-lazertinib-chemotherapy, chemotherapy alone, or amivantamab-chemotherapy. The primary endpoint was PFS by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1). Secondary endpoints included objective response rate (ORR), intracranial PFS, and safety. Due to mid-study modifications to the amivantamab-lazertinib-chemotherapy dosing schedule, follow-up of this group is ongoing. We present results for the amivantamab-chemotherapy vs. chemotherapy arms in the Asian subgroup. Results There were 190 participants in the Asian subgroup, 63 in the amivantamab-chemotherapy group and 127 in the chemotherapy group. At a median follow-up of 9.5 months, median PFS in the amivantamab-chemotherapy arm was 6.8 vs. 4.2 months in the chemotherapy arm [hazard ratio (HR) 0.54, 95% confidence interval (CI): 0.37–0.81; nominal P=0.002]. The ORR was 66% and 32%, respectively (odds ratio 4.0, 95% CI: 2.1–7.7; nominal P<0.001) and median intracranial PFS was 12.5 and 8.5 months (HR 0.58, 95% CI: 0.34–1.00; nominal P=0.049). The safety profile in the Asian subgroup was in line with the overall MARIPOSA-2 population. Conclusions Amivantamab-chemotherapy demonstrated superior PFS vs. chemotherapy in Asian patients. Amivantamab-chemotherapy provides an effective option for patients whose disease had progressed on third-generation EGFR tyrosine kinase inhibitors.