Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study

被引：452

作者：

Park, Keunchil ^{[1
]}

Haura, Eric B. ^{[2
]}

Leighl, Natasha B. ^{[3
]}

Mitchell, Paul ^{[4
]}

Shu, Catherine A. ^{[5
]}

Girard, Nicolas ^{[6
]}

Viteri, Santiago ^{[7
]}

Han, Ji-Youn ^{[8
]}

Kim, Sang-We ^{[9
]}

Lee, Chee Khoon ^{[10
]}

Sabari, Joshua K. ^{[11
]}

Spira, Alexander, I ^{[12
]}

Yang, Tsung-Ying ^{[13
]}

Kim, Dong-Wan ^{[14
,15
]}

Lee, Ki Hyeong ^{[16
]}

Sanborn, Rachel E. ^{[17
]}

Trigo, Jose ^{[18
]}

Goto, Koichi ^{[19
]}

Lee, Jong-Seok ^{[20
]}

Yang, James Chih-Hsin ^{[21
]}

Govindan, Ramaswamy ^{[22
]}

Bauml, Joshua M. ^{[23
]}

Garrido, Pilar ^{[24
]}

Krebs, Matthew G. ^{[25
,26
]}

Reckamp, Karen L. ^{[27
]}

Xie, John ^{[28
]}

Curtin, Joshua C. ^{[28
]}

Haddish-Berhane, Nahor ^{[28
]}

Roshak, Amy ^{[28
]}

Millington, Dawn ^{[28
]}

Lorenzini, Patricia ^{[28
]}

Thayu, Meena ^{[28
]}

Knoblauch, Roland E. ^{[28
]}

Cho, Byoung Chul ^{[29
]}

机构：

[1] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Seoul, South Korea

[2] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[3] Princess Margaret Canc Ctr, Toronto, ON, Canada

[4] Austin Hosp, Olivia Newton John Canc Wellness & Res Ctr, Heidelberg, Vic, Australia

[5] Columbia Univ, Med Ctr, New York, NY USA

[6] Inst Curie, Paris, France

[7] Hosp Univ Dexeus, Inst Oncol Dr Rosell, Grp QuironSalud, Barcelona, Spain

[8] Natl Canc Ctr, Gyeonggi Do, South Korea

[9] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea

[10] St George Hosp, Kogarah, NSW, Australia

[11] NYU, Sch Med, New York, NY USA

[12] Virginia Canc Specialists Res Inst, US Oncol Res, Fairfax, VA USA

[13] Taichung Vet Gen Hosp, Taichung, Taiwan

[14] Seoul Natl Univ, Coll Med, Seoul, South Korea

[15] Seoul Natl Univ Hosp, Seoul, South Korea

[16] Chungbuk Natl Univ Hosp, Cheongju, South Korea

[17] Providence Canc Inst, Earle A Chiles Res Inst, Portland, OR USA

[18] Hosp Univ Virgen de la Victoria & Reg, IBIMA, Malaga, Spain

[19] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan

[20] Seoul Natl Univ, Bundang Hosp, Seongnam, South Korea

[21] Natl Taiwan Univ, Canc Ctr, Taipei, Taiwan

[22] Washington Univ, Sch Med, St Louis, MO USA

[23] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[24] Hosp Univ Ramon y Cajal, IRYCIS, Madrid, Spain

[25] Univ Manchester, Fac Biol Med & Hlth, Div Canc Sci, Manchester, Lancs, England

[26] Christie NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[27] City Hope Comprehens Canc Ctr, Duarte, CA USA

[28] Janssen R&D, Spring House, PA USA

[29] Yonsei Univ, Yonsei Canc Ctr, Coll Med, Seoul, South Korea

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2021年 / 39卷 / 30期

关键词：

GROWTH-FACTOR RECEPTOR; BISPECIFIC ANTIBODY; GENE-MUTATIONS; TRIAL; JNJ-61186372; GEFITINIB; CMET;

D O I：

10.1200/JCO.21.00662

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 = 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. CONCLUSION Arnivantamab, 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. (C) 2021 by American Society of Clinical Oncology

引用

页码：3391 / 3402

页数：12

共 35 条

[1] EGFR Exon 20 Insertion Mutations in Lung Adenocarcinomas: Prevalence, Molecular Heterogeneity, and Clinicopathologic Characteristics [J].

Arcila, Maria E. ;

Nafa, Khedoudja ;

Chaft, Jamie E. ;

Rekhtman, Natasha ;

Lau, Christopher ;

Reva, Boris A. ;

Zakowski, Maureen F. ;

Kris, Mark G. ;

Ladanyi, Marc .

MOLECULAR CANCER THERAPEUTICS, 2013, 12 (02) :220-229

[2]

Bauml JM, 2021, J THORAC ONCOL, V16, pS208

[3] Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network [J].

Beau-Faller, M. ;

Prim, N. ;

Ruppert, A. -M. ;

Nanni-Metellus, I. ;

Lacave, R. ;

Lacroix, L. ;

Escande, F. ;

Lizard, S. ;

Pretet, J. -L ;

Rouquette, I. ;

de Cremoux, P. ;

Solassol, J. ;

de Fraipont, F. ;

Bieche, I. ;

Cayre, A. ;

Favre-Guillevin, E. ;

Tomasini, P. ;

Wislez, M. ;

Besse, B. ;

Legrain, M. ;

Voegeli, A. -C. ;

Baudrin, L. ;

Morin, F. ;

Zalcman, G. ;

Quoix, E. ;

Blons, H. ;

Cadranel, J. .

ANNALS OF ONCOLOGY, 2014, 25 (01) :126-131

[4] Amivantamab (JNJ-61186372), an EGFR-MET bispecific antibody, in combination with lazertinib, a 3rd-generation tyrosine kinase inhibitor (TKI), in advanced EGFR NSCLC [J].

Cho, B. C. ;

Lee, K. H. ;

Cho, E. K. ;

Kim, D-W. ;

Lee, J-S. ;

Han, J-Y. ;

Kim, S-W. ;

Spira, A. ;

Haura, E. B. ;

Sabari, J. K. ;

Sanborn, R. E. ;

Bauml, J. M. ;

Gomez, J. E. ;

Lorenzini, P. ;

Infante, J. R. ;

Xie, J. ;

Haddish-Berhane, N. ;

Thayu, M. ;

Knoblauch, R. E. ;

Park, K. .

ANNALS OF ONCOLOGY, 2020, 31 :S813-S813

[5]

Cho BC, 2018, ANN ONCOL, V29

[6] Real-World Treatment Patterns and Survival in Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations [J].

Dersarkissian, M. ;

Bhak, R. ;

Lin, H. ;

Li, S. ;

Cheng, M. ;

Lax, A. ;

Huang, H. ;

Duh, M. ;

Ou, S. .

JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (10) :S681-S681

[7] Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial [J].

Garon, Edward B. ;

Ciuleanu, Tudor-Eliade ;

Arrieta, Oscar ;

Prabhash, Kumar ;

Syrigos, Konstantinos N. ;

Goksel, Tuncay ;

Park, Keunchil ;

Gorbunova, Vera ;

Dario Kowalyszyn, Ruben ;

Pikiel, Joanna ;

Czyzewicz, Grzegorz ;

Orlov, Sergey V. ;

Lewanski, Conrad R. ;

Thomas, Michael ;

Bidoli, Paolo ;

Dakhil, Shaker ;

Gans, Steven ;

Kim, Joo-Hang ;

Grigorescu, Alexandru ;

Karaseva, Nina ;

Reck, Martin ;

Cappuzzo, Federico ;

Alexandris, Ekaterine ;

Sashegyi, Andreas ;

Yurasov, Sergey ;

Perol, Maurice .

LANCET, 2014, 384 (9944) :665-673

[8] Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy [J].

Hanna, N ;

Shepherd, FA ;

Fossella, FV ;

Pereira, JR ;

De Marinis, F ;

von Pawel, J ;

Gatzemeier, U ;

Tsao, TCY ;

Pless, M ;

Muller, T ;

Lim, HL ;

Desch, C ;

Szondy, K ;

Gervais, R ;

Shaharyar ;

Manegold, C ;

Paul, S ;

Paoletti, P ;

Einhorn, L ;

Bunn, PA .

JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (09) :1589-1597

[9]

Haura EB, 2019, J CLIN ONCOL, V37

[10] A Phase II Study of Bevacizumab, Oxaliplatin, and Capecitabine in Patients With Previously Untreated Metastatic Colorectal Cancer A Prospective, Multicenter Trial of the Korean Cancer Study Group [J].

Hong, Yong Sang ;

Lee, Sung Sook ;

Kim, Kyu-pyo ;

Lee, Jae-Lyun ;

Kang, Yoon-Koo ;

Shin, Sang Joon ;

Ahn, Joong Bae ;

Jung, Kyung Hae ;

Im, Seock-Ah ;

Kim, Tae-You ;

Kim, Jee Hyun ;

Park, Young Suk ;

Kim, Tae Won .

AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2014, 37 (01) :19-23

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