Amivantamab in Patients with Advanced NSCLC and MET Exon 14 Skipping Mutation: Results from the CHRYSALIS Study

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oregon; chiles


Introduction: Amivantamab, an epidermal growth factor receptor (EGFR)/ mesenchymal-epithelial transition factor (MET) bispecific antibody with immune cell-directing activity, is approved for the treatment of advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations after prior platinum-based chemotherapy. In an earlier report, amivantamab demonstrated encouraging antitumor activity in patients with advanced NSCLC and primary MET exon 14 skipping mutation (METex14) and a safety profile consistent with the larger CHRYSALIS (NCT02609776) population (Krebs JCO 2022; 40:16_suppl, 9008). Here we present updated results of a larger METex14 patient population from the CHRYSALIS study. Methods: CHRYSALIS, an ongoing phase 1 study of amivantamab in advanced NSCLC, enrolled patients with primary METex14 whose disease progressed on or who declined the current regional standard-of-care therapy. Patients were treated with amivantamab monotherapy at the approved dose (1050 mg or 1400 mg if ≥80 kg) weekly for the first 4 weeks (cycle 1) and biweekly thereafter. Response was assessed by investigator per RECIST v1.1. Circulating tumor DNA (ctDNA) was collected at baseline, during treatment and at the end of treatment for exploratory resistance profiling. Results: As of 22 Feb 2023, 97 patients with primary METex14 received amivantamab and had ≥1 postbaseline disease assessment(s) or discontinued for any reason. Median age was 70 (range, 43-88) years, 54% were women, 48% Asian and 39% White, and 14% had baseline brain metastases. The median follow-up was 7.9 months; 16 were treatment naïve, 28 were previously treated but had no prior MET inhibitor, and 53 had a prior MET inhibitor. Objective response rate (ORR) was 33% in the overall population; ORR was 56% in treatment-naïve patients, 46% in patients with no prior MET inhibitor, and 19% in patients with prior MET inhibitors. Across the 32 responders, the median duration of response (DOR) was 11.2 (95% CI, 4.3-19.1) months; 14 had DOR ≥6 months and 15 were ongoing treatment. Among the 49 patients with stable disease, all but 1 demonstrated reduction in tumor size. The overall clinical benefit rate (CBR) was 69%; CBR was 88% in treatment-naïve patients, 64% in patients with no prior MET inhibitor, and 66% in patients with prior MET inhibitors. Most common treatment-emergent adverse events (TEAEs) were rash (76%), infusion-related reaction (72%), and paronychia (45%). Forty-one (42%) patients experienced TEAEs of grade ≥3 severity, which were reported as related to treatment in 19 (20%). Treatment-related dose interruptions, reductions, and discontinuations occurred in 24 (25%), 11 (11%), and 8 (8%) patients, respectively. Grade ≥3 AEs leading to treatment-related discontinuations were pneumonitis, infusion-related reaction, peripheral edema, and dyspnea (1 patient each). Analysis of ctDNA resistance patterns and updated response data will be provided at the time of meeting. Conclusions: In this larger patient population, amivantamab demonstrated antitumor activity in NSCLC patients with primary METex14, including those who failed MET inhibitors. Safety profile was consistent with the previously reported experience of amivantamab in EGFR-driven NSCLC.

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Leighl N, Cho BC, Hiret S, Han J-Y, Lee KH, Perez CL, Krebs MG, Braud FD, Haura E, Sanborn RE, Yang JC-H, Shu CA, Goto K, Nishio M, Zhao J, Wang Z, Tomasini P, Felip E, Goldman JW, Ou S-HI, Boyer M, Gao G, Qu S, Curtin JC, Lyu X, Schnepp ARRW, Kim P, Mertz J, Thayu M, Shreeve SM, Knoblauch RE, Spira AI. IASLC 2023 World Lung Cancer Conference; September 9-12; Singapore. 2023: OA21.04.

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