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Amivantamab in Participants With Advanced NSCLC and MET Exon 14 Skipping Mutations: Final Results From the CHRYSALIS
Matthew G Krebs1, Byoung Chul Cho2, Sandrine Hiret3
1Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom.
Introduction:
Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity. We assessed the safety and efficacy of amivantamab in participants with advanced NSCLC harboring primary MET exon 14 skipping mutations (METex14).
Methods:
CHRYSALIS enrolled participants with METex14 NSCLC who progressed after or declined standard-of-care therapy. Participants received intravenous amivantamab weekly for 4 weeks and biweekly thereafter. Objective response rate, duration of response (DoR), clinical benefit rate, progression-free survival, overall survival, safety, and circulating tumor DNA were analyzed.
Results:
Among 97 participants, 16 were treatment naive, 28 received prior treatment without MET therapies, and 53 received prior MET therapies. Objective response rate was 32% overall, 50% in treatment-naive participants, 46% in participants without prior MET therapies, and 19% in participants with prior MET therapies. In participants without prior MET therapies, amivantamab activity was observed regardless of co-occurring genomic alterations. Clinical benefit rate was 69% overall, 88% in treatment-naive participants, 64% in participants without prior MET therapies, and 66% in participants with prior MET therapies. Median DoR was 11.2 months; 61% (19/31) of the responders had DoR greater than or equal to 6 months. Median progression-free survival was 5.3 months (95% confidence interval, 4.3-7.0); median overall survival was 15.8 months (95% confidence interval, 14.6-not estimable). Most common adverse events were rash (79%) and infusion-related reactions (72%), most being grades 1 to 2 (52%).
Conclusions:
The safety profile was consistent with previous reports of amivantamab in EGFR-mutant NSCLC. Amivantamab demonstrated clinically meaningful and durable antitumor activity in participants with METex14 advanced NSCLC, including those who progressed on prior MET therapies.
Insights
Amivantamab shows significant antitumor activity in advanced non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations. This bispecific antibody offers durable responses, even in patients previously treated with MET therapies.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- Amivantamab is an epidermal growth factor receptor (EGFR)-MET bispecific antibody.
- It targets advanced non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations (METex14).
Purpose of the Study:
- To assess the safety and efficacy of amivantamab in patients with advanced METex14 NSCLC.
- Evaluate amivantamab's activity in treatment-naïve and previously treated populations.
Main Methods:
- The CHRYSALIS trial enrolled patients with METex14 NSCLC.
- Patients received amivantamab intravenously, with dosing adjustments.
- Key endpoints included objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- Amivantamab demonstrated an overall ORR of 32%, with higher rates in treatment-naïve (50%) and previously untreated (46%) patients.
- Median DoR was 11.2 months, with 61% of responders having responses lasting ≥6 months.
- Median PFS was 5.3 months and median OS was 15.8 months. Common adverse events included rash and infusion-related reactions, mostly grade 1-2.
Conclusions:
- Amivantamab exhibits clinically meaningful and durable antitumor activity in advanced METex14 NSCLC.
- The safety profile is consistent with prior amivantamab studies.
- Amivantamab is effective even in patients who progressed on prior MET therapies.
