Details

Autor(en) / Beteiligte

• Park, Keunchil
• Haura, Eric B
• Leighl, Natasha B
• Mitchell, Paul
• Shu, Catherine A
• Girard, Nicolas
• Viteri, Santiago
• Han, Ji-Youn
• Kim, Sang-We
• Lee, Chee Khoon
• Sabari, Joshua K
• Spira, Alexander I
• Yang, Tsung-Ying
• Kim, Dong-Wan
• Lee, Ki Hyeong
• Sanborn, Rachel E
• Trigo, José
• Goto, Koichi
• Lee, Jong-Seok
• Yang, James Chih-Hsin
• Govindan, Ramaswamy
• Bauml, Joshua M
• Garrido, Pilar
• Krebs, Matthew G
• Reckamp, Karen L
• Xie, John
• Curtin, Joshua C
• Haddish-Berhane, Nahor
• Roshak, Amy
• Millington, Dawn
• Lorenzini, Patricia
• Thayu, Meena
• Knoblauch, Roland E
• Cho, Byoung Chul

Titel

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

Ist Teil von

• Journal of clinical oncology, 2021-10, Vol.39 (30), p.3391-3402

Ort / Verlag

United States: Wolters Kluwer Health

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor ( ) 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 Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum 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 Exon20ins mutations after progression on platinum-based chemotherapy.