P2.09-35 Amivantamab vs Real World Therapies for Advanced NSCLC with EGFR Exon20ins in China

Introduction: Epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations are generally associated with poor prognosis and resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (aNSCLC). In the single-arm CHRYSALIS study (NCT02609776), patients with aNSCLC and EGFR Exon20ins demonstrated durable responses to amivantamab, a bispecific antibody targeting EGFR and mesenchymal epithelial transition factor (MET) with immune-directing activity. Since CHRYSALIS is a non-randomized study, this study aims to evaluate the clinical benefits of amivantamab among patients with Exon20ins in CHRYSALIS in comparison to systemic anti-cancer therapy (SACT) in a real-world external cohort (EC) in China. Methods: CHRYSALIS patients who were previously treated with platinum-based chemotherapy, met eligibility criteria, and received the recommended Phase 2 dose of amivantamab were included. A clinically similar EC cohort was identified from a lung cancer multi-center electronic medical records (EMR) database (LC-ME) and Shanghai Chest hospital (SCH). Adult patients who were diagnosed with aNSCLC between March 2015 to July 2020, tested positive for Exon20ins mutation, previously treated with platinum-based chemotherapy, and had at least one SACT after Exon20ins diagnosis were included in the EC. EC patients were included for every qualifying line of therapy (LoT) after platinum-based chemotherapy. Average treatment effect on the treated was used to minimize the confounding bias through adjustment for age, gender, smoking status and number of prior lines of therapy (LoT). Outcomes were compared between EC and CHRYSALIS patients using weighted Cox proportional hazards regression models for progression-free survival (PFS), time to next therapy (TTNT) and overall survival (OS), and using generalized estimating equations with repeated measurements for overall response rate (ORR). Results: A total of 115 CHRYSALIS patients and 41 patients (87 LoT after platinum-based chemotherapy) from EC were included in this analysis. The median PFS were 6.74 [5.49-8.31] and 5.62 [3.88-9.26] months for CHRYSALIS and EC, hazard ratio (HR) 0.77 [0.52-1.13] (P=0.175). The median TTNT for CHRYSALIS and EC were 12.16 [8.61-19.35] and 6.08 [4.27-9.46] months respectively, HR 0.52 [0.35-0.76] (P<0.001). The median OS for CHRYSALIS and EC were 19.88 and 13.47 months with HR of 0.65 [0.35-1.20] (P=0.171). However, a higher ORR was observed in CHRYSALIS compared to EC (41.7% vs. 1.5%) with Odds Ratio of 45.80 [9.87-212.64] (P<0.001). Conclusions: The EC identified from the real-world setting in China enables comparative effectiveness analysis on the clinical benefits of amivantamab. The results showed that aNSCLC patients with Exon20ins who received amivantamab had significantly improved TTNT and higher ORR than those who received current real-world therapies, while PFS and OS were numerically better. TTNT is considered to be a better evaluation of effectiveness in this real-world study because of the limited completeness of records for disease progression from the EC data source. The results also showed the clinical benefit of amivantamab after platinum chemotherapy for aNSCLC Exon20ins patients and indicates that amivantamab should be a standard of care of this specific population. Keywords: NSCLC, Exon 20 insertion, Amivantamab