Amivantamab plus chemotherapy versus chemotherapy for first-line treatment of participants with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer: PAPILLON Asia subgroup analysis

Background: Amivantamab is a bispecific, epidermal growth factor receptor (EGFR) and MET-proto-oncogene (MET)-targeting antibody with immune cell-directing activity. In the global Phase 3 PAPILLON trial, amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) significantly improved progression-free survival (PFS) vs chemotherapy alone in previously untreated participants with locally advanced/metastatic NSCLC with EGFR exon 20 insertions (Ex20ins). We evaluated clinical outcomes in Asian participants in PAPILLON (NCT04538664). Methods: Participants were randomized 1:1 to amivantamab-chemotherapy or chemotherapy alone. Study endpoints for this analysis were PFS by blinded independent central review (primary), objective response rate (ORR), duration of response (DoR), PFS after first subsequent therapy (PFS2), overall survival (OS), and safety (secondary). Crossover to amivantamab monotherapy was allowed when disease progressed on chemotherapy alone. Results: Among 186 participants in the Asian sub-cohort, 97 received amivantamab-chemotherapy and 89 received chemotherapy. At median follow-up of 16.6 months, median PFS (95% confidence interval [CI]) in the amivantamab-chemotherapy/chemotherapy groups was 11.5/5.6 months (hazard ratio [HR] 0.34; 95%CI, 0.23–0.49; nominal p < 0.0001) arms. The ORR was 70% vs 51% (odds ratio 2.2, 95%CI, 1.2–3.9; nominal p = 0.012), DoR 10.1 vs 5.5 months. Median PFS2 was not estimable vs 18.8 months (HR 0.46, 95%CI 0.26–0.83; nominal p = 0.008), and median interim OS not estimable vs 24.4 months HR 0.65, 95%CI 0.34–1.24; nominal p = 0.189), respectively, despite substantial (73%) crossover. Safety profiles for both arms were similar to the overall PAPILLON population. Conclusions: Amivantamab-chemotherapy demonstrated superior PFS vs chemotherapy and represents a new standard of care for first-line treatment of Asian participants with Ex20ins-mutated NSCLC.