Park, KeunchilHaura, Eric BLeighl, Natasha BMitchell, PaulShu, Catherine AGirard, NicolasViteri, SantiagoHan, Ji-YounKim, Sang-WeLee, Chee KhoonSabari, Joshua KSpira, Alexander IYang, Tsung-YingKim, Dong-WanLee, Ki HyeongSanborn, Rachel ETrigo, JoséGoto, KoichiLee, Jong-SeokYang, James Chih-HsinGovindan, RamaswamyBauml, Joshua MGarrido, PilarKrebs, Matthew GReckamp, Karen LXie, JohnCurtin, Joshua CHaddish-Berhane, NahorRoshak, AmyMillington, DawnLorenzini, PatriciaThayu, MeenaKnoblauch, Roland ECho, Byoung Chul2025-01-072025-01-072021-08-02https://hdl.handle.net/10668/27014Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site. CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with EGFR Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum EGFR Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5. In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively. Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with EGFR Exon20ins mutations after progression on platinum-based chemotherapy.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/AdultAgedAged, 80 and overAntibodies, BispecificAntineoplastic Agents, ImmunologicalCarcinoma, Non-Small-Cell LungDiarrheaDisease ProgressionDrug EruptionsErbB ReceptorsExonsFemaleHumansHypokalemiaInjection Site ReactionLung NeoplasmsMaleMiddle AgedMutagenesis, InsertionalNeutropeniaOrganoplatinum CompoundsParonychiaProgression-Free SurvivalPulmonary EmbolismRetreatmentAmivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.research article34339292open access10.1200/JCO.21.006621527-7755PMC8791812https://ascopubs.org/doi/pdfdirect/10.1200/JCO.21.00662https://pmc.ncbi.nlm.nih.gov/articles/PMC8791812/pdf