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 - Funding Information:
This study was funded by Janssen R&D LLC M.G.K. acknowledges support from National Institute for Health Research (NIHR) Manchester Biomedical Research Centre and NIHR Manchester Clinical Research Facility at The Christie and Manchester Experimental Cancer Medicine Centre (Manchester, United Kingdom). Medical writing assistance was funded by Janssen Global Services LLC and provided by Tracy T. Cao, PhD (Janssen Global Services LLC).
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 -