Patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC following EGFR TKI and platinum-based chemotherapy: HERTHENA-Lung01 Meeting Abstract

  


Authors: Yu, H. A.; Yasushi, G.; Hidetoshi, H.; Felip, E.; Chih-Hsin Yang, J.; Reck, M.; Yoh, K.; Lee, S. H.; Paz-Ares, L.; Besse, B.; Bironzo, P.; Kim, D. W.; Johnson, M. L.; Wu, Y. L.; Dong, Q.; Fan, P. D.; Shrestha, P.; Sternberg, D. W.; Sellami, D.; Jänne, P. A.
Abstract Title: Patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC following EGFR TKI and platinum-based chemotherapy: HERTHENA-Lung01
Meeting Title: 14th Annual Navigation & Survivorship Conference of the Academy of Oncology Nurse And Patient Navigators (AONN+)
Abstract: Background: For patients with epidermal growth factor receptor (EGFR)-mutated non--small cell lung cancer (NSCLC) posttreatment with EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC), safe and effective new therapies are needed. In a phase 1 study (NCT03260491), patritumab deruxtecan, U3-1402 (HER3- DXd), showed promising efficacy and a manageable safety profile in patients with advanced EGFR-mutated NSCLC following an EGFR TKI and PBC. Objective: HER3-DXd is an antibody-drug conjugate consisting of a fully human monoclonal antibody to HER3 attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. Here, we report data from the phase 2 HERTHENA-Lung01 trial (NCT04619004). Methods: This open-label study included patients with advanced EGFR-mutated NSCLC previously treated with an EGFR TKI and PBC. Patients were randomized to receive 1 of 2 dose schedules of HER3-DXd: 5.6 mg/kg IV Q3W or an up-titration regimen (3.2 mg/kg→4.8 mg/ kg→6.4 mg/kg). Enrollment in the up-titration arm closed early based on a benefit-risk assessment of emerging phase 1 data; enrollment in the 5.6-mg/kg arm was completed. The primary endpoint was confirmed ORR by blinded independent central review (BICR) per RECIST version 1.1. Intracranial responses were measured by BICR per CNS RECIST. Results: Two hundred twenty-five patients received HER3-DXd 5.6 mg/kg. As of May 18, 2023, median study duration was 18.9 months (range, 14.9-27.5 mo). Confirmed ORR by BICR was 29.8% (95% CI, 23.9%-36.2%); median DOR, 6.4 months (95% CI, 4.9-73.8); PFS, 5.5 months (95% CI, 5.1-5.9); and OS, 11.9 months (95% CI, 11.2- 13.1). Patients with prior osimertinib had similar outcomes. Activity was observed across a broad range of HER3 expression and diverse mechanisms of EGFR TKI resistance. In patients with nonirradiated brain metastases (n=30), confirmed CNS ORR was 33.3% (95% CI, 17.3%- 52.8%; 9/30 CR, 1/30 PR); DCR was 76.7%. At the primary data cutoff (November 21, 2022), median treatment duration was 5.5 months (range, 0.7-18.2 mo). Adverse events (AEs) were manageable and tolerable: Drug-related AEs were associated with discontinuation in 10 patients (4.4%) and death in 4 (1.8%); 45.3% had grade (G) ≥3 drug-related AEs; 12 patients (5.3%) had independently adjudicated drug-related interstitial lung disease (G1/2, n=9; G3, n=2; G5, n=1). Conclusions: In this patient population with significant unmet need and limited therapeutic options, HER3-DXd demonstrated clinically meaningful efficacy; moreover, this study provides the first report of HER3-DXd efficacy in the CNS. The safety profile was manageable and consistent with previous observations. Overall, HER3-DXd is a promising therapy for patients with previously treated EGFR-mutated NSCLC. A phase 3 trial in EGFR-mutated NSCLC after progression on EGFR TKI is ongoing (HERTHENA-Lung02; NCT05338970). Funding: This study was funded by Daiichi Sankyo.
Keywords: mutation; texas; chemotherapy, cancer; antibodies, monoclonal -- therapeutic use; enzyme inhibitors -- therapeutic use; carcinoma, non-small-cell lung -- drug therapy; epidermal growth factor receptors; tyrosine kinase inhibitors -- therapeutic use; platinum -- therapeutic use; congresses and conferences -- texas; drug efficacy -- evaluation
Journal Title: Journal of Oncology Navigation & Survivorship
Volume: 14
Issue: 11
Meeting Dates: 2022 Nov 15-19
Meeting Location: San Antonio, TX
ISSN: 2166-0999
Publisher: Green Hill HealthCare Communications, LLC  
Date Published: 2023-11-01
Start Page: 362
Language: English
PROVIDER: EBSCOhost
PROVIDER: cinahl
DOI/URL:

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Notes: Meeting abstract: A13 -- Source: Cinahl