2019 ASCO Annual Meeting!
Session: EGFR and ROS1: Targeting Resistance
Type: Clinical Science Symposium
Time: Friday May 31, 1:00 PM to 2:30 PM
Location: Hall D1
Safety and preliminary antitumor activity of U3-1402: A HER3-targeted antibody drug conjugate in EGFR TKI-resistant, EGFRm NSCLC.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9010)
Author(s): Pasi A. Janne, Helena Alexandra Yu, Melissa Lynne Johnson, Conor Ernst Steuer, Michele Vigliotti, Corinne Iacobucci, Shuquan Chen, Channing Yu, Dalila B. Sellami; Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Sarah Cannon Research Institute, Nashville, TN; Winship Cancer Institute of Emory University, Atlanta, GA; Daiichi Sankyo, Inc., Basking Ridge, NJ
Background: Treatment options are limited for EGFRm NSCLC resistant to EGFR TKIs. HER3 is expressed in a majority of NSCLC tumors. U3-1402 is a HER3-targeted antibody drug conjugate with a fully human HER3-targeted antibody, novel cleavable peptide-based linker, and topoisomerase I inhibitor payload. Methods: An ongoing multicenter phase 1 dose escalation and expansion study is assessing U3-1402 safety/tolerability and preliminary activity in metastatic or unresectable EGFRm NSCLC patients (pts) who are T790M negative after disease progression while on erlotinib, gefitinib or afatinib; or develop disease progression while on osimertinib regardless of T790M status. Dose escalation is based on dose-limiting toxicities (DLTs) and guided by the modified Continuous Reassessment Method. U3-1402 is administered via intravenous infusion in 21-day cycles. Pretreatment tumor tissue is required. Results: As of 11 Nov 2018, 15 pts (6 M; 9 F) were enrolled across 3 dose levels (3.2, 4.8, 6.4 mg/kg). Median age was 63 y; 10 pts had EGFR exon 19 deletion and 5 EGFR L858R mutation. Median sum of longest diameters (SLD) at baseline was 69 (range 22–143) mm. All pts had prior EGFR TKIs; 14 had 2nd line or later osimertinib. Six had prior chemotherapy. All 11 evaluable tumors demonstrated HER3 expression (median HER3 membrane H-score 188, range 150–290). Five pts discontinued treatment: 4 due to progressive disease, 1 due to adverse event (AE). All Grade (Gr) treatment-emergent AEs (TEAEs) in ≥20% of pts were nausea (60%), vomiting (40%), fatigue (33%), decreased appetite (27%), and alopecia (20%). Gr≥3 TEAEs were nausea (1/15; Gr3; related), hypoxia (1/15; Gr3; unrelated), and platelet count decreased (2/15; both Gr4 at 6.4 mg/kg and considered DLTs). In 13 evaluable pts, all but 1 had a decrease in SLD (median best change −29%, range +10% to −67%), 2 had confirmed partial response per RECIST v1.1 (best changes −44%, −67%). Conclusions: U3-1402 showed a manageable safety profile and preliminary antitumor activity in EGFR TKI-resistant EGFRm NSCLC. Evaluation of candidate biomarkers, including HER3 expression, which correlate with U3-1402 response is ongoing. Clinical trial information: NCT03260491