The Phase 2b COPERNICUS Study of Subcutaneous Amivantamab with Lazertinib as First-Line Treatment, or with...

In advanced non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations (Ex19del/L858R), intravenous amivantamab is approved for first-line treatment with lazertinib, and second-line treatment with carboplatin-pemetrexed. Subcutaneous amivantamab demonstrated noninferior pharmacokinetics and comparable efficacy with improved safety outcomes versus intravenous amivantamab in the PALOMA-3 trial. Venous thromboembolism (VTE) was also reduced when combined with prophylactic anticoagulation. In the COCOON trial, an enhanced prophylactic dermatologic regimen with intravenous amivantamab plus lazertinib treatment lowered grade ≥ 2 dermatologic adverse events (AEs). There are no studies combining subcutaneous administration with supportive care advancements in diverse participants with EGFR-mutated NSCLC. COPERNICUS (NCT06667076), an open-label, phase 2b study aims to evaluate the efficacy and safety of subcutaneous amivantamab with lazertinib (cohort 1) or with chemotherapy (cohort 2) while preventing and proactively managing VTE and dermatologic AEs in a multinational, clinically representative population with EGFR-mutated NSCLC.

Eligible participants are adults with EGFR Ex19del/L858R NSCLC. A pragmatic study approach will be used to eliminate potential barriers to enrollment and increase diversity. Cohort 1 will enroll participants without prior systemic therapy to receive subcutaneous amivantamab and oral lazertinib. Cohort 2 will enroll participants with disease progression on EGFR-tyrosine kinase inhibitors to receive subcutaneous amivantamab and chemotherapy (carboplatin-pemetrexed). Both cohorts will receive enhanced dermatologic management; cohort 1 will receive prophylactic anticoagulation for the first 4 months of treatment. The primary endpoint is investigator-assessed progression-free survival.

COPERNICUS is currently enrolling, with a planned enrollment in the United States of 300 and 30 participants in cohorts 1 and 2, respectively, plus 150 participants for cohort 1 in Europe.

COPERNICUS uses a pragmatic study design to evaluate the efficacy and safety of subcutaneous amivantamab regimens combined with advancements in supportive care to prevent and proactively manage AEs in a diverse participant population. Supplementary file1 (MP4 117333 KB).