COPERNICUS, a pragmatic phase 2b study of subcutaneous (SC) amivantamab (ami) + chemotherapy (chemo) with enhanced dermatologic adverse event (AE) prophylaxis in <i>EGFR</i> -mutated advanced NSCLC: Interim results.

Abstract

8614 Background: In MARIPOSA-2, intravenous ami + carboplatin-pemetrexed chemo significantly prolonged progression-free survival (PFS) vs chemo (HR, 0.48; P &lt;0.001) in participants (pts) with EGFR -mutated (exon 19 deletion [Ex19del]/L858R) advanced NSCLC after progression on osimertinib. However, longer infusion times, infusion-related reactions (59%), and dermatologic AEs (paronychia [37%], rash [43%]) were observed, with frequent interruptions of ami due to AEs (60%) as a potential result. Numerous studies have since tested ways to optimize ami administration. PALOMA-3/-2 showed reductions in administration-related reactions (ARRs) and administration time with SC ami coformulated with hyaluronidase (rHuPH20), thus enhancing patient experience and leading to approval by the FDA/EMA. COCOON also showed fewer grade ≥2 dermatologic AEs vs standard of care with an enhanced prophylactic regimen. Methods: COPERNICUS (NCT06667076) is the first study to combine SC ami and optimized supportive care, using a pragmatic design to broaden the pt population and better resemble real-world usage. We report planned interim results of Cohort 2 for SC ami every 3 weeks (Q3W) + chemo on/after EGFR TKI progression in US pts with EGFR Ex19del/L858R NSCLC receiving dermatologic AE prophylaxis aligned with the regimen described in COCOON. Pragmatic design included partnering with academic/community sites and less stringent eligibility criteria to enhance pt diversity. Primary endpoint is PFS by investigator. Key secondary endpoints are overall response rate (ORR) and safety, including incidence/severity of dermatologic AEs and ARRs. All comparisons to MARIPOSA-2 are descriptive. Results: As of data cutoff (02 Jan 2026), 29 pts had enrolled in Cohort 2 (target enrollment, 30; median [range] follow-up: 7.6 [0.5+–10.2] mo); 76% were still ongoing in the study. Median age was 62 y, with 45% of pts ≥65 y and 21% ≥75 y; 38% were Asian and 7% African American. Median PFS was 7.4 mo (95% CI, 4.8–NE; Table). AEs were mostly grade 1–2, with no new safety signals; 31% of pts interrupted ami due to AEs. With dermatologic prophylaxis, paronychia and rash occurred in 24% and 14% of pts, respectively, showing numerical reductions vs MARIPOSA-2. ARRs (grouped term) were also numerically lower at 21%. Conclusions: Compared with MARIPOSA-2, SC ami and dermatologic prophylaxis in COPERNICUS led to substantial reductions in ARRs, dermatologic AEs, and ami interruptions, establishing the positive effect of early supportive care interventions. These interim data obtained using a pragmatic design support wide use of SC ami Q3W + chemo post-EGFR TKI progression in a diverse population. Clinical trial information: NCT06667076 . Median PFS, mo (95% CI) 7.4 (4.8–NE) ORR (95% CI) 24.1% (10.3–43.5) Partial response 7 (24.1%) Stable disease 15 (51.7%) Progressive disease 2 (6.9%)