Amivantamab in patients with NSCLC with MET exon 14 skipping mutation: Updated results from the CHRYSALIS study.

Abstract

9008 Background: Amivantamab, a fully human bispecific antibody targeting epidermal growth factor receptor (EGFR) and MET, is approved for the treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion after prior platinum-based chemotherapy. Given its bispecific nature, amivantamab is being explored in patients (pts) with primary MET exon 14 skipping mutation (METex14) in the MET-2 cohort of the CHRYSALIS study. Methods: CHRYSALIS (NCT02609776) is an ongoing phase 1 dose escalation/dose expansion study of amivantamab in pts with advanced NSCLC. Pts with primary METex14 whose disease progressed on or who declined current standard of care therapy were treated with amivantamab 1050 mg (pts <80 kg) or 1400 mg (pts ≥80 kg) weekly in cycle 1 and biweekly thereafter. Response was assessed by investigators using RECIST v1.1. Results: As of 2 Dec 2021, 43 pts with METex14 had received amivantamab. Median age was 70 y (range, 43-88), 58% were women, median prior lines of therapy was 2 (range, 0-10) [eg, crizotinib (n=13), capmatinib (n=11), tepotinib (n=5), anti-MET antibody (n=1)], and 23% had history of brain metastases at baseline. In 36 pts with ≥1 postbaseline disease assessment, median duration of follow-up was 5.8 months (range, 0.3-15.8); 6 pts had no prior treatment, 11 had no prior MET inhibitor, and 19 had a prior MET inhibitor. Overall response rate was 33% (50% [3/6] in treatment-naïve pts, 46% [5/11] in pts with no prior MET inhibitor, and 21% [4/19] in pts with prior MET inhibitor therapy). Clinical benefit rate was >54% regardless of prior treatment (Table). Median duration of response (DOR) was not reached (range, 2.1-12.2 months); 67% (8/13) had DOR ≥6 months. Ten of the 12 responders remain on treatment (6.0-14.4 months) with ongoing responses; 2 discontinued after 2 and 12 months, respectively. Safety profile was consistent with previously reported experience of amivantamab (Sabari 2021 JTO 16(3):S108-109). Treatment-related adverse events leading to dose reduction or discontinuation occurred in 3 pts, each. Conclusions: Amivantamab demonstrates anti-tumor activity in primary METex14 NSCLC including after prior MET inhibitor treatment. Enrollment is ongoing and updated data will be shown. Clinical trial information: NCT02609776. [Table: see text]

Meeting an un-MET need: Targeting MET in non-small cell lung cancer

“…To date, 11 of the 15 patients who responded to amivantamab remain on treatment. These results suggest that amivantamab has anti-tumor activity for both EGFR and MET-altered NSCLC (43).…”

Brief Report: First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)

“…ORR was 68% (95% CI, 48-84) in 20 evaluable patients, PFS was 12.6 months (95%CI=[5.6 -NR]) and median DoR was Patients received 2 (range, 0-10) prior lines of therapy in median. In 36 evaluable patients, overall response rate was 33% (50% [3/6] in treatment-naïve patients, 46% [5/11] in patients with no prior MET inhibitor, and 21% [4/19] in patients with prior MET inhibitor therapy) (16). Nevertheless PD-L1 status was not reported in these 3 studies, as well as ICI treatment.…”

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

“…For patients of treatment naïve population, the PFS and OS of savolitinib were 6.9 months and 10.9 months, respectively, while PFS and OS of prior treatment patients reached 6.9 months and 19.4 months, respectively. In the current scenario, the reported ORR of savolitinib is the highest in the prior treatment population compared to other treatments (52.6% vs. 44.0% of capmatinib, 49.5% of tepotinib and 21% of amivantamab) [ 48 , 62 , 63 , 64 ]. Savolitinib is also currently the only MET inhibitor that has recorded beneficial OS data in brain metastases, with PFS of 7.0 months and OS of 17.7 months.…”

“…Table 5 summarizes the data for MET-TKIs developed for MET ex14-altered advanced NSCLC population as well as subtypes [ 4 , 38 , 47 , 48 , 58 , 59 , 62 , 63 , 64 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Patient population of Chinese Phase II registry trial were from China.…”

“…Tumor response of different types of MET–TKIs shows ORR (54.8%) and DCR (92.9%) to be highest with savolitinib. Among AEs, most commonly, elevated transaminases were seen with savolitinib, tepotinib and crizotinib; peripheral edema with savolitnib, capmatinib and tepotinib; ILD with capmitnib, tepotinib and crizotinib; difficulty in breathing in tepotinib, crizotinib and amivantamab [ 38 , 48 , 58 , 59 , 62 , 63 , 64 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ].…”