KEY TAKEAWAYS
- A Phase I study assessed amivantamab in advanced NSCLC pts with primary METex14 mutations who either progressed on or declined standard-of-care therapy.
- Amivantamab showed efficacy in treating NSCLC pts with primary METex14 mutations, with a safety profile consistent with earlier EGFR-mutated NSCLC studies.
Amivantamab, a bispecific antibody targeting EGFR and MET with immune cell-directing capabilities, has received approval for treating advanced NSCLC with specific EGFR mutations following platinum-based chemotherapy.
Earlier findings indicated its promising antitumor effects and acceptable safety in NSCLC patients (pts) with primary MET exon 14 skipping mutations (METex14) as part of the broader CHRYSALIS study. Researchers presented updated data on a larger METex14 patient group from the CHRYSALIS trial.
The ongoing CHRYSALIS Phase 1 study enrolled NSCLC pts exhibiting primary METex14 mutations who either showed disease progression or declined existing standard-of-care treatments. These pts received monotherapy of amivantamab at approved doses (1050 mg or 1400 mg for those weighing ≥80 kg), administered weekly during the initial four-week cycle and biweekly afterward. Tumor response was evaluated by investigators following RECIST v1.1 guidelines. Circulating tumor DNA (ctDNA) samples were collected at various stages, including baseline, therapy, and treatment conclusion.
As of February 22, 2023, 97 NSCLC pts with primary METex14 mutations were administered amivantamab and subsequently assessed. The median age was 70 years, with a demographic makeup of 54% women, 48% Asian, 39% White, and 14% having baseline brain metastases. The median follow-up stood at 7.9 months. Objective Response Rates (ORRs) were observed as follows: 33% overall, 56% in treatment-naïve patients, 46% in those without prior MET inhibitors, and 19% in those with prior MET inhibitors.
Among the 32 responders, the median Duration of Response (DOR) was 11.2 months. Clinical Benefit Rate (CBR) was 69% overall. Treatment-emergent adverse events (TEAEs) included rash (76%), infusion-related reactions (72%), and paronychia (45%), with 42% experiencing grade ≥3 severity. Treatment modifications due to adverse events occurred in a subset of patients. Future analysis will include ctDNA resistance patterns.
The extended data confirmed that amivantamab effectively treats NSCLC pts with primary METex14 mutations, even among those previously treated with MET inhibitors. Its safety profile aligns with prior experiences in EGFR-mutated NSCLC.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/996
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02609776
Leighl, N., Cho, B.C., Hiret, S., Han, J-Y., Lee, K.H., Perez, C.L., Krebs, M.G., De Braud, F., Haura, E., Sanborn, R.E., Yang, J.C-H., Shu, C.A., Goto, K., Nishio, M., Zhao, J., Wang, Z., Tomasini, P., Felip, E., Goldman, J.W., Ou, S-H.I., Boyer, M., Gao, G., Qu, S., Curtin, J.C., Lyu, X., Roshak, A., Schnepp, R.W., Kim, P., Mertz, J., Thayu, M., Shreeve, S.M., Knoblauch, R.E., Spira, A.I. Amivantamab in Patients with Advanced NSCLC and MET Exon 14 Skipping Mutation: Results from the CHRYSALIS Study.
