What is the Origami trial about, specifically in relation to non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions and the use of amivantamab?

The ORIGAMI Trial

I was unable to locate information about a trial specifically named "ORIGAMI" in the provided evidence related to non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions and amivantamab.

Relevant Trials for EGFR Exon 20 Insertion NSCLC with Amivantamab

Based on the available evidence, the key clinical trials evaluating amivantamab in this population are:

PAPILLON Trial (Phase III)

This is the pivotal first-line trial that established amivantamab plus chemotherapy as the preferred treatment for EGFR exon 20 insertion NSCLC. 1

• Design: Phase III randomized trial comparing amivantamab plus carboplatin-pemetrexed versus chemotherapy alone in 308 treatment-naïve patients with advanced NSCLC harboring EGFR exon 20 insertions 1

• Key Results:

  • Median PFS: 11.4 months (amivantamab-chemotherapy) vs 6.7 months (chemotherapy alone); HR 0.40, P < 0.001 1
  • Overall response rate: 67% vs 36% 2
  • At 18 months, 31% remained progression-free with amivantamab-chemotherapy vs 3% with chemotherapy alone 3
  • Interim OS analysis showed HR 0.67 (P = 0.11) 1

• Safety Profile: Most common adverse events were hematologic effects and EGFR-related toxicities (rash, paronychia, dermatitis acneiform) 1

• Regulatory Impact: Based on PAPILLON, NCCN recommends amivantamab-vmjw plus carboplatin-pemetrexed as a Category 1 and preferred first-line treatment option for advanced or metastatic nonsquamous EGFR exon 20 insertion mutation-positive NSCLC 1

CHRYSALIS Trial (Phase I)

This trial established amivantamab monotherapy for post-platinum EGFR exon 20 insertion NSCLC 1

• Design: Phase I study evaluating amivantamab monotherapy in 81 patients with EGFR exon 20 insertion-positive metastatic NSCLC who had received one or more prior lines of therapy 1

• Key Results:

  • Overall response rate: 40% (including 3 complete responses) 1
  • Median PFS: 8.3 months 1
  • Median duration of response: 11.1 months 4

• Safety Profile: Common treatment-related adverse events included cutaneous reactions (86%), infusion-related reactions (66%), and paronychia (45%) 1, 4

  • Most common grade 3-4 adverse events: hypokalemia, pulmonary embolism, neutropenia, diarrhea, and rash 1
  • Eight deaths (7%) reported in safety assessment 1

• Regulatory Impact: Based on CHRYSALIS, amivantamab-vmjw received FDA approval as monotherapy for adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertions whose disease progressed on or after platinum-based chemotherapy 1

Clinical Context

EGFR exon 20 insertions represent a historically difficult-to-treat subset of EGFR-mutant NSCLC, with resistance to early-generation EGFR TKIs (gefitinib, erlotinib, afatinib showing ORRs of only 3-8%) 1. Amivantamab, as a bispecific EGFR-MET antibody, bypasses this resistance by targeting the extracellular domains of both receptors 4.

If you were referring to a different trial name or have additional context about "ORIGAMI," please clarify so I can provide more specific information.