1192MO Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: Analysis from the CHRYSALIS study

Abstract

Amivantamab (ami), an epidermal growth factor receptor (EGFR)-MET bispecific antibody, has demonstrated efficacy in EGFR mutant non-small cell lung cancer (NSCLC) that progressed on osimertinib (osi), both as monotherapy and in combination with lazertinib (laz), a 3rd-generation tyrosine kinase inhibitor. Clinical outcomes of patients (pts) treated with ami monotherapy (mono) and ami in combination with laz (combo) are presented here. CHRYSALIS is an ongoing study of ami in pts with advanced EGFR mutant NSCLC (NCT02609776). Pts who progressed on osi were pooled to form the mono group, a majority of whom were preselected for C797S/other resistance mutations or MET amplification. The combo group comprised unselected pts who had progressed on osi but were chemotherapy-naïve. Response was assessed by the investigator per RECIST v1.1. As of 19 Apr 2021, 121 pts in the mono group (85% with EGFR/MET-based resistance) and 45 in the combo group (38% with EGFR/MET-based resistance) were efficacy-evaluable, with median follow-up of 6.9 and 11.1 months, respectively. Antitumor activity was observed in the mono group, with 33 achieving partial response (PR) as best response, of which 23 were confirmed, for an overall response rate (ORR) of 19% (95% CI, 12–27). In the combo group, 1 complete response and 15 PRs were observed, all of which confirmed, for an ORR of 36% (95% CI, 22–51). Median duration of response was 5.9 months with mono, 9.6 months with combo (Table). The safety profile for both mono and combo was consistent with previously-reported safety. No new safety signals were identified. Antitumor activity of ami + laz in the post-osi setting appears favorable even without molecular selection post osimertinib failure, supporting that simultaneous targeting of the extracellular and catalytic domains of EGFR provides additive benefits.Table: 1192MOEfficacy of amivantamab monotherapy and in combination with lazertinib among efficacy-evaluablea patientsEfficacyMonotherapy (n=121)Combination (n=45)ORR (95% CI)19% (12–27)36% (22–51)CBR (95% CI)48% (39–57)64% (49–78)mDOR, month (95% CI)5.9 (4.2–12.6)9.6 (5.3–NR)aPatients who had at least 2 post-baseline disease assessment or discontinued before the second assessment. CBR, clinical benefit rate (complete response, partial response, or stable disease of at least 11 weeks); mDOR, median duration of response; ORR, overall response rate; NR, not reached Open table in a new tab