TY - JOUR
T1 - Amivantamab in egfr exon 20 insertion- mutated non-small-cell lung cancer progressing on platinum chemotherapy
T2 - Initial results from the chrysalis phase i study
AU - Park, Keunchil
AU - Haura, Eric B.
AU - Leighl, Natasha B.
AU - Mitchell, Paul
AU - Shu, Catherine A.
AU - Girard, Nicolas
AU - Viteri, Santiago
AU - Han, Ji Youn
AU - Kim, Sang We
AU - Lee, Chee Khoon
AU - Sabari, Joshua K.
AU - Spira, Alexander I.
AU - Yang, Tsung Ying
AU - Kim, Dong Wan
AU - Lee, Ki Hyeong
AU - Sanborn, Rachel E.
AU - Trigo, Jose
AU - Goto, Koichi
AU - Lee, Jong Seok
AU - Chih-Hsin Yang, James
AU - Govindan, Ramaswamy
AU - Bauml, Joshua M.
AU - Garrido, Pilar
AU - Krebs, Matthew G.
AU - Reckamp, Karen L.
AU - Xie, John
AU - Curtin, Joshua C.
AU - Haddish-Berhane, Nahor
AU - Roshak, Amy
AU - Millington, Dawn
AU - Lorenzini, Patricia
AU - Thayu, Meena
AU - Knoblauch, Roland E.
AU - Cho, Byoung Chul
N1 - Publisher Copyright:
© 2021 American Society of Clinical Oncology. All rights reserved.
PY - 2021/10/20
Y1 - 2021/10/20
N2 - PURPOSE Non-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. METHODS 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. RESULTS In the efficacy population (n 5 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 5 114), 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. CONCLUSION 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.
AB - PURPOSE Non-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. METHODS 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. RESULTS In the efficacy population (n 5 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 5 114), 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. CONCLUSION 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.
UR - http://www.scopus.com/inward/record.url?scp=85112311967&partnerID=8YFLogxK
U2 - 10.1200/JCO.21.00662
DO - 10.1200/JCO.21.00662
M3 - Article
C2 - 34339292
AN - SCOPUS:85112311967
SN - 0732-183X
VL - 39
SP - 3391
EP - 3402
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -