Real-world outcomes of amivantamab monotherapy in advanced EGFR-mutant non-small cell lung cancer.

e20717 Background: Amivantamab, a bispecific EGFR/MET antibody, is approved for EGFR exon 20 insertion-mutant non-small cell lung cancer (NSCLC). However, real-world data evaluating it as monotherapy beyond exon 20 variants remain limited, as most retrospective series include combination therapy or heterogeneous settings. In clinical practice, some patients may receive monotherapy due to toxicity concerns, comorbidities, prior treatment tolerance, or physician/patient preference. We evaluated clinical outcomes of amivantamab monotherapy in a real-world cohort of patients with EGFR-mutant NSCLC. Methods: We conducted an IRB-approved retrospective review (Pro2025-0001) of patients with advanced EGFR-mutant NSCLC treated with amivantamab monotherapy in the second line or later between June 2021 and September 2024. Patients were categorized as classical (exon 19 deletion or L858R), atypical (eg, exon 18 or G719X), or exon 20 insertion (ex20ins), and unspecified variants. Analyses evaluated progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), time to next treatment (TTNT), overall survival (OS), and safety. Radiographic response was assessed by investigator review using RECIST v1.1. Time-to-event outcomes were censored at last assessment on or before September 30, 2024. Confidence intervals (CIs) were calculated using exact binomial methods for proportions and Kaplan-Meier methods for time-to-event endpoints. Results: Twenty-two patients met inclusion criteria; median age was 67.5 years (range, 42-82), and patients were heavily pretreated (median prior therapies, 2). Baseline CNS metastases were present in 36%. Mutation subgroups included 13 classical, 5 atypical, and 3 exon 20 insertions, and 1 unclassified variant. Twenty patients were evaluable for response. ORR was 25.0% (95% CI, 8.7-49.1) and DCR was 60.0% (95% CI, 36.1-80.9). ORR/DCR were 25%/75% in classical EGFR (3/12), 40%/40% in atypical EGFR (2/5), and 0%/33% in ex20ins (0/3), though subgroup estimates were limited by small sample size. Median PFS was 4.2 months (95% CI, 1.35-7.29). Median TTNT was 5.2 months. Median OS was 10.7 months (95% CI, 2.9-31.3) from amivantamab initiation and 35.4 months (95% CI, 25.8-74.0) from initial diagnosis. Median follow-up was 27.8 months. Grade ≥3 treatment-related adverse events occurred in 2 patients, including hyponatremia, peripheral edema, and infusion reaction. Intracranial progression occurred in 7 of 11 patients with evaluable CNS imaging (64%). Conclusions: In this heavily pretreated real-world cohort, amivantamab monotherapy demonstrated meaningful antitumor activity across diverse EGFR mutation subtypes, with outcomes comparable to prior trials and real-world experiences. These findings support consideration of amivantamab monotherapy beyond exon 20 insertions and warrant prospective evaluation in defined clinical settings.