3MO Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutant advanced NSCLC after progression on osimertinib: A post-progression analysis of MARIPOSA-2

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. In MARIPOSA-2 (NCT04988295), ami plus carboplatin-pemetrexed (ami-chemo) significantly prolonged progression-free survival (PFS) vs chemo in patients (pts) with EGFR-mutant advanced NSCLC after progression on osimertinib (Passaro Ann Oncol 2023). Post-progression outcomes from MARIPOSA-2 were assessed. 657 pts were randomized. These analyses focus on the 131 pts randomized to ami-chemo (safety: n=130) and 263 to chemo (safety: n=243). A third arm (ami-lazertinib-chemo) was modified and will be reported in the future. Post-progression endpoints were time to treatment discontinuation (TTD), time to subsequent therapy (TTST), and PFS after first subsequent therapy (PFS2). At a median follow-up of 8.7 months (mo), 55/130 (42%) pts in the ami-chemo arm and 173/243 (71%) in the chemo arm had progressive disease (PD). Among those with PD, 19/55 (35%) in the ami-chemo arm and 28/173 (16%) in the chemo arm were treated beyond progression for >4 weeks with a median (95% CI) post-progression treatment duration of 18.3 (9.0–NE) and 9.0 (6.0–16.4) weeks, respectively. Compared to chemo, ami-chemo significantly prolonged TTD (median, 11.0 vs 4.5 mo for chemo; HR, 0.37 95% CI, 0.28–0.50; P<0.0001), TTST (median, 12.1 vs 6.6 mo for chemo; HR, 0.42 95% CI, 0.30–0.59; P<0.0001), and PFS2 (median, 13.9 vs 11.3 mo for chemo; HR, 0.60 95% CI, 0.40–0.92; P=0.017). Among pts with PD, including pts treated beyond PD, 75% (41/55) in the ami-chemo arm discontinued treatment after progression vs 93% (161/173) for chemo. 63% of pts with PD initiated subsequent systemic therapy in both arms. Most common subsequent therapies were osimertinib (ami-chemo:10%; chemo: 9%) and docetaxel (ami-chemo: 7%; chemo: 9%). Ami-chemo significantly prolonged TTD, TTST, and PFS2 vs chemo. Ami-chemo represents the new standard of care for pts with EGFR-mutant advanced NSCLC after PD on osimertinib.