Abstract
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.
(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.
| Original language | English |
|---|---|
| Journal | Journal of Clinical Oncology |
| DOIs | |
| Publication status | Published - 2 Aug 2021 |
Research Beacons, Institutes and Platforms
- Manchester Cancer Research Centre
