COPERNICUS, a pragmatic phase 2b study of first-line (1L) subcutaneous (SC) amivantamab (ami) + lazertinib (laz) with supportive care in <i>EGFR</i> -mutated advanced NSCLC: Early safety results.

Abstract

8613 Background: In MARIPOSA, intravenous (IV) ami + laz significantly prolonged overall survival vs osimertinib (HR, 0.75; P =0.005) in 1L EGFR -mutated (exon 19 deletion [Ex19del]/L858R) advanced NSCLC. However, extended infusion times, infusion-related reactions (63%), venous thromboembolism (VTE; 36%), and dermatologic adverse events (AEs; paronychia [68%], rash [62%]) were observed, potentially leading to discontinuations of ami due to AEs (34%). Several studies have since identified ways to optimize ami + laz administration. In PALOMA-3/-2, SC ami coformulated with hyaluronidase (rHuPH20) enhanced patient (pt) experience by reducing administration-related reactions (ARRs) and time, as well as VTE with prophylactic anticoagulation, leading to FDA/EMA approval. In COCOON, an enhanced dermatologic regimen reduced grade ≥2 dermatologic AEs vs standard of care. Methods: COPERNICUS (NCT06667076) is the first study to combine SC ami, optimized supportive care and a pragmatic design to broaden the pt population and better resemble real-world usage. This is an early report from Cohort 1 on pt demographics and safety of SC ami every 4 weeks (Q4W) + laz daily in pts with 1L EGFR Ex19del/L858R advanced NSCLC receiving VTE/dermatologic AE prophylaxis. Pragmatic design included partnering with academic/community sites to enhance pt diversity, allowing 1 cycle of 1L chemotherapy while awaiting biomarker results and using SC ami Q4W to reduce visit frequency. Pts received prophylactic anticoagulation for the first 4 months of treatment. Dermatologic prophylaxis aligned with the regimen described in COCOON. Here we report safety (key secondary endpoint), including incidence/severity of VTE, ARRs and dermatologic AEs. All comparisons to MARIPOSA are descriptive. Results: As of data cutoff (02 Jan 2026), Cohort 1 had enrolled 190 pts in the US (target enrollment, 300; median [range] follow-up, 3.9 [0.1–11.7] mo); 92% were still ongoing in the study. Median age was 66 y, with 55% of pts ≥65 y and 21% ≥75 y; 28% were Asian and 9% African American, reflecting broad enrollment. 6 pts had received 1 chemotherapy cycle. AEs were mostly grade 1–2, with no new safety signals; 5% discontinued ami due to AEs. With dermatologic prophylaxis, paronychia and rash were 26% and 22%, respectively, showing numerical reductions vs MARIPOSA. ARRs and VTE (both grouped terms) were also numerically lower at 9% and 7%, respectively. Conclusions: Compared with MARIPOSA, SC ami and dermatologic/VTE prophylaxis in COPERNICUS substantially reduced ARRs, dermatologic AEs, VTE, and ami discontinuations, highlighting the impact of early supportive care interventions. Using a pragmatic design, these early safety data support wide use of SC ami Q4W + laz in a diverse population. Given limited follow up, pts will continue to be evaluated for safety and efficacy. Clinical trial information: NCT06667076 .