5MO Effect of amivantamab dose interruptions on efficacy and safety of first-line amivantamab plus lazertinib in EGFR-mutant advanced NSCLC: Exploratory analyses from the MARIPOSA study

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant 3rd-generation EGFR TKI. As first-line treatment, ami+laz demonstrated superior progression-free survival (PFS) vs osimertinib in patients (pts) with EGFR-mutant advanced non-small cell lung cancer (NSCLC; Cho Ann Oncol 2023). Protocol guidance in the MARIPOSA study (NCT04487080) recommended an ami dose interruption in the case of related grade ≥2 toxicity. For pts treated with first-line ami+laz, the majority of key adverse events occurred in the first 4 months (mo; Spira JTO 2023). We studied the efficacy and safety in ami+laz pts that had ami dose interruptions in the first 4 months. This analysis included all pts who were randomized to the ami+laz arm in MARIPOSA (efficacy set: n=429, safety set: n=421). Study protocol dictated ami to be dose modified before laz. Dose interruptions were defined as any interruptions of ami due to any cause. Among the 429 pts who were randomized to the ami+laz arm, 421 received at least one dose. At a median follow-up of 22.0 months, 49% (206/421) had ami dose interruptions in the first 4 months of treatment. Among pts who required ami dose interruptions in the first 4 months, the median PFS was 23.9 mo (95% CI, 18.5–NE). Median PFS, objective response rate (ORR), and median duration of response (DoR) for pts with and without dose interruptions of ami in the first 4 months were similar to all pts randomized to the ami+laz arm, as shown in the table. Updated analyses, including the impact of dose interruptions on treatment tolerability, will be presented at the time of the meeting.Table: 5MOEfficacy endpoints among patients with and without ami dose interruptions within the first 4 months of receiving Ami+LazMedian (95% CI)Dose interruptions in the first 4 months (n=206)No dose interruptions in the first 4 months (n=215)All patients (n=429)PFS23.9 mo (18.5–NE)23.7 mo (18.4–NE)23.7 mo (19.1–27.7)6 months*88 (82-91)86 (81-90)87 (83-90)12 months*71 (64-77)75 (69-81)73 (69-77)18 months*60 (52-66)60 (53-66)60 (55-64)ORR87% (81–91)89% (84–93)86% (83–89)DoR among confirmed responders25.8 mo (16.7–NE)26.1 mo (20.1–NE)25.8 mo (20.1–NE)CI, confidence interval; NE, not estimable *Event-free rate shown as percentage (95%CI) Open table in a new tab CI, confidence interval; NE, not estimable *Event-free rate shown as percentage (95%CI) Among pts receiving ami+laz, early dose modifications of ami per protocol guidance did not adversely impact the efficacy of the combination. Ami+laz is a new first-line standard of care for pts with EGFR-mutant advanced NSCLC.