Amivantamab in non-small cell lung cancer (NSCLC) with MET Exon 14 skipping (METex14) mutation: initial results from CHRYSALIS
Krebs, Matthew G
Cho, B. C.
Lee, C. K.
Trigo, J. M.
AffiliationVirginia Cancer Specialists Research Institute, Usoncology Research, Fairfax/VA/US
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AbstractIntroduction:Amivantamab, a novel, fully human bispecific antibodytargeting both the epidermal growth factor receptor (EGFR) and MET,is being explored as a monotherapy in non-small cell lung cancer(NSCLC) within the CHRYSALIS study (NCT02609776), and hasreceived Breakthrough Therapy Designation for the treatment of patients with EGFR exon 20 insertion disease, after prior treatmentwith platinum chemotherapy. Given the bispecific nature of amivanta-mab, its role in patients with MET exon 14 skipping (METex14) mu-tations is being explored (MET-2 cohort) in patients both naïve to andrefractory to other available MET therapy. We present early resultsdemonstrating amivantamab activity in MET-driven NSCLC.Methods:CHRYSALIS is an ongoing phase 1 dose escalation/dose expansionstudy of amivantamab in patients with advanced NSCLC. Patients withMETex14 NSCLC whose disease progressed on or who declined currentstandard of care were treated at the recommended phase 2 dose(RP2D) of 1050 mg (1400 mg 80 kg) weekly in cycle 1 and biweeklythereafter. Response was assessed by the investigator using RECISTv1.1.Results:As of 29 Mar 2021, 16 patients with METex14 NSCLChad received amivantamab at the RP2D. Median age was 70 (range,55e75), 69% were women, and median prior lines of therapy were 2(range, 0e10), including prior treatment with crizotinib (n¼3), cap-matinib (n¼1), tepotinib (n¼2), and anti-MET antibody (n¼1). Ninepatients had at least 1 postbaseline disease assessment, 7 are pendingfirst disease assessment; 13 remain on treatment. Antitumor activitywas observed in each of the 9 response-evaluable patients, with 4confirmed partial responses, including patients with prior anti-METtherapy (Figure). Three of the 4 responders remain on treatment(6.0e6.6+ months) with ongoing responses, and 1 discontinued after12 months. The safety profile was consistent with previously reportedexperience of amivantamab at the RP2D (Sabari 2021JTO16(3):S108-109). Treatment-related adverse events leading to dose reduction ordiscontinuation occurred in 6% of patients, each. Among 7 patientswho received prior MET tyrosine kinase inhibitor (TKI), baseline ctDNAdemonstrated 2 patients with potential resistance mechanisms: PIK3CAmutation in one, and CDK4 and EGFR amplifications and a possiblesecondary MET mutation (A1251V) in the other. Five patients had noidentified MET TKI resistance alteration.Conclusion:This reportprovidesfirst evidence of amivantamab activity in MET-driven NSCLC,in addition to its previously reported anti-EGFR activity, consistentwith its bispecific mechanism of action. Enrollment into MET-2 cohortis ongoing, and presentation will include updated data.
CitationSpira A, Krebs M, Cho BC, Besse B, Goldman J, Janne P, et al. OA15.03 Amivantamab in Non-small Cell Lung Cancer (NSCLC) with MET Exon 14 Skipping (METex14) Mutation: Initial Results from CHRYSALIS [Internet]. Vol. 16, Journal of Thoracic Oncology. Elsevier BV; 2021. p. S874–5.
JournalJournal of Thoracic Oncology