Abstract CT233: A phase 2b study of subcutaneous amivantamab with lazertinib as first-line treatment, or with chemotherapy as second-line treatment, for <i>EGFR</i>-mutated non-small cell lung cancer (NSCLC): COPERNICUS

Abstract Background: Intravenous (IV) amivantamab is approved in combination with lazertinib for first-line (1L) NSCLC with EGFR Exon 19 deletions (Ex19del) or L858R substitution mutations, and in combination with chemotherapy for second-line (2L) EGFR Ex19del/L858R NSCLC, based on the favorable efficacy and safety results of the phase 3 MARIPOSA and MARIPOSA-2 clinical trials. Subcutaneous (SC) amivantamab demonstrated noninferior efficacy and improved safety vs IV amivantamab in the phase 3 PALOMA-3 study. Furthermore, a prophylactic anticoagulation regimen for venous thromboembolism (VTE) prevention and an enhanced regimen for managing dermatologic toxicities were validated in PALOMA-3 and the phase 2 COCOON study, respectively. However, no study has combined SC amivantamab with these advancements in supportive care in a representative, diverse group of participants with advanced EGFR-mutated NSCLC in the US. The open-label, 2-cohort, phase 2b COPERNICUS study (NCT06667076) aims to enroll a participant population that is demographically reflective of the overall US prevalence of EGFR-mutated NSCLC and to evaluate the efficacy and safety of SC amivantamab with lazertinib (Cohort 1) or chemotherapy (Cohort 2) while preventing and proactively managing VTE and dermatologic adverse events (AEs). Methods: Eligible participants are adults (≥18 years old) whose tumors harbor EGFR Ex19del or L858R. In Cohort 1, participants must not have received any prior systemic therapy and will receive SC amivantamab and oral lazertinib; in Cohort 2, participants must have had disease progression after EGFR-TKI monotherapy and will receive SC amivantamab and chemotherapy (carboplatin-pemetrexed). Both cohorts will receive enhanced dermatologic management, and Cohort 1 will receive prophylactic anticoagulation for the first 4 months of treatment. The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include incidence and severity of VTE and dermatologic AEs, overall survival, objective response rate, duration of response, and compliance with prophylactic medications. Results: COPERNICUS is currently enrolling, with a planned enrollment of 300 and 30 participants in Cohorts 1 and 2, respectively. Conclusion: COPERNICUS aims to evaluate the efficacy and safety of SC amivantamab regimens using a pragmatic study design to enroll participants with diverse backgrounds and combine advancements in supportive care to prevent and proactively manage AEs. Citation Format: Balazs Halmos, Narjust Florez, Sarah Goldberg, Wade Iams, Xiuning Le, Ticiana Leal, Danny Nguyen, Luis E. Raez, Jonathan W. Riess, Joshua Sabari, David Bjork, Nichelle Stigger, Yichuan Xia, Paul Cifuentes, Denise D’Andrea, Andy L. Johnson, Melissa L. Johnson. A phase 2b study of subcutaneous amivantamab with lazertinib as first-line treatment, or with chemotherapy as second-line treatment, for EGFR-mutated non-small cell lung cancer (NSCLC): COPERNICUS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT233.