Bifalgorithm post · ASCO 2026: Studies Aim to Expand Treatment Options for Lung Cancer · CHRYSALIS-2: First-Line Amivantamab Plus Lazertinib

Study Design

Study Design (ASCO 2026: Studies Aim to Expand Treatment Options for Lung Cancer · CHRYSALIS-2: First-Line Amivantamab Plus Lazertinib) — "The findings come fr…

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  • Findings from CHRYSALIS-2 Cohort C
  • Open-label, multinational phase 2b dose-expansion cohort (NCT04077463)
  • The cohort enrolled 49 treatment-naïve patients with locally advanced or metastatic NSCLC and atypical EGFR mutations.
  • Patients with Ex20ins and Ex19del/L858R co-mutations were excluded.
  • Baseline patient and tumor characteristics
  • Median age was 60 years; 45% of patients were female and 57% were Asian.
  • EGFR mutations included G619X (55%), S768X (27%), and L861X (24%); 35% of tumors had compound mutations.
  • Afatinib, the only currently approved therapy, has an overall survival of less than 2 years.
  • The investigated combination was amivantamab plus lazertinib.
  • Amivantamab is an EGFR plus MET bispecific monoclonal antibody.
  • Lazertinib is a third-generation EGFR tyrosine kinase inhibitor.
  • Treatment consisted of intravenous amivantamab plus daily oral lazertinib.
  • Amivantamab was given weekly during cycle 1, with the first dose split over 2 days, then every 2 weeks.
  • Amivantamab dosing was 1050 mg, or 1400 mg for patients weighing at least 80 kg; day 1 included 350 mg.
  • Lazertinib was administered orally at 240 mg daily.
  • The regimen used complementary mechanisms of action.
  • Dual EGFR inhibition
  • MET inhibition
  • Immune cell direction
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ASCO 2026: Studies Aim to Expand Treatment Options for Lung Cancer

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"The findings come from an analysis of dose-expansion Cohort C of the open-label, multi-cohort, multinational phase 2b CHRYSALIS-2 study (NCT04077463). The researchers enrolled 49 treatment-naïve patients with locally advanced or metastatic NSCLC harboring atypical EGFR mutations, excluding patients with Ex20ins and Ex19del/L858R co-mutations.\n\nAt baseline, the cohort’s median age was 60 years; 45% of patients were female and 57% were Asian. EGFR mutations included G619X (55%), S768X (27%), and L861X (24%), with 35% of tumors showing compound mutations, Dr Neal reported.\n\n“The only currently approved therapy, afatinib, has an overall survival of less than 2 years,” Dr Neal explained. “We looked at a new therapy, amivantamab, which is an EGFR plus MET bispecific monoclonal antibody, plus lazertinib, which is a third-generation EGFR tyrosine kinase inhibitor, in combination.”\n\nPatients received intravenous amivantamab (1050 mg, or 1400 mg for patients weighing at least 80 kg) once weekly in cycle 1, with the first dose split over 2 days (350 mg on day 1), then every 2 weeks, plus daily oral lazertinib (240 mg). The regimen’s mechanisms of action included dual EGFR inhibition, MET inhibition, and immune cell direction."

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