11P Patritumab deruxtecan (HER3-DXd) in previously treated patients (pts) with advanced EGFR-mutated (EGFRm) NSCLC: Updated safety results from HERTHENA-Lung01

Tolerable therapies are needed for previously treated pts with advanced EGFRm NSCLC. The ph 2 HERTHENA-Lung01 trial (NCT04619004) showed meaningful efficacy and a manageable safety profile. To extend these safety observations, we present data with an additional 6 mo of follow-up. Pts (N=225) previously treated with EGFR TKI and platinum-based chemotherapy received HER3-DXd 5.6 mg/kg IV Q3W. Median treatment (TX) duration was 5.5 (range, 0.7-23.7) mo. 224 pts (99.6%) had any-grade (G) TEAEs; 147 (65.3%) had G ≥3. Most common any-G TEAEs were nausea (66.2%), thrombocytopenia (43.6%), and decreased appetite (42.2%); most common G ≥3 were thrombocytopenia (20.9%), neutropenia (19.1%), and anemia (15.1%). 88.9% of pts had a GI TEAE; 8% had a G ≥3 event. Incidence of GI TEAEs generally decreased over the course of TX. 2 pts (0.9%) experienced G ≥3 bleeding unrelated to TX within ±14 d of G ≥3 decreased platelet count. 2 pts (0.9%) experienced G ≥3 infections unrelated to TX within ±14 d of G ≥3 decreased neutrophil count. Febrile neutropenia occurred in 7 pts (3.1%; all G ≥3). G-CSF was used to manage neutropenia in 23 pts (10.2%). 14 pts (6.2%) had centrally adjudicated TX-related interstitial lung disease (G 1/2, n=9; G 3, n=4; G 5, n=1); 2 events occurred in the 6-mo follow-up. Median time to onset and duration were 70.5 (range, 9-474) and 40 (range, 6-207) d. 4 pts had TX-related TEAEs associated with death (pneumonitis, GI perforation, pneumonia, respiratory failure n=1 each). TEAEs associated with dose interruption occurred in 41.3% of pts, dose reduction in 22.2%, and discontinuation in 8.4%. Hematologic AEs occurred early in TX, were transient, and managed by dose modifications and supportive care. No pts discontinued TX due to thrombocytopenia; 20 (8.9%) received platelet transfusions. Anemia was associated with TX discontinuation in 1 pt (0.4%); 28 (12.4%) received RBC transfusions. HER3-DXd demonstrated a manageable safety profile, consistent with previous reports. Hematologic and GI TEAEs typically occurred in early TX cycles. No additional safety signals were observed.