921MO Phase I global study of Iza-Bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and other solid tumors

H.A. Yu; X. Le; M.L. Johnson; N. Iannotti; A.I. Spira; P.A. Jänne; M. Furqan; T. Patil; G. Lopes; C.A. Perez; W.J. Edenfield; S.V. Liu; Z. Piotrowska; C. Park; J.L. Zhao; H. Wang; G. Russo; H. Zhu; J. Cheng; J. Peguero

doi:10.1016/j.annonc.2025.08.1490

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921MO Phase I global study of Iza-Bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and other solid tumors

Abstract

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921MO Phase I global study of Iza-Bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and other solid tumors

H.A. Yu, X. Le, M.L. Johnson, N. Iannotti, A.I. Spira, P.A. Jänne, M. Furqan, T. Patil, G. Lopes, C.A. Perez, …

Annals of oncology, Vol.36(Suppl 2), pp.S601-S602

09/2025

DOI: 10.1016/j.annonc.2025.08.1490

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Abstract

Background Iza-bren is a potential first-in-class ADC comprised of an EGFR x HER3 bispecific antibody conjugated to a novel topoisomerase 1 inhibitor payload (Ed-04) via a stable tetrapeptide-based cleavable linker. Results of dose escalation/ finding phase from this global phase 1 BL-B01D1-LUNG-101 study are presented. Methods Iza-bren was given at 1.5, 2.0, 2.3, 2.5, 3.0 mg/kg D1D8 Q3W, or 3.0, 4.0, 4.5 mg/kg D1 Q3W. Pts were not selected for EGFR or HER3 expression. G-CSF support is optional. Results As of March 20, 2025, 113 pts, including 82 NSCLC, 7 small cell lung cancer (SCLC), 17 breast cancer (BC), 5 esophageal adenocarcinoma (EAC) and 2 others, were treated with iza-bren. Median prior line of therapy was 3 (range 1-10). The most frequent treatment-related adverse events (TRAEs) (all grades/ grade ≥3) were hematologic, including neutropenia (66%/ 55%), anemia (50%/ 28%), and thrombocytopenia (33%/ 12%); the most frequent non-hematologic TRAEs were fatigue (45%), alopecia (40%), nausea (39%), and diarrhea (35%), and predominantly low grades. Hematologic AEs were effectively managed as TRAE leading to dose reduction was 21.2% and discontinuation was 1.8%. No interstitial lung disease (ILD) was observed. Efficacy from D1D8 Q3W (selected for further development) is summarized in the table. Promising efficacy was observed at 2.5 mg/kg in multiple tumor types with confirmed ORR (cORR) of 55.0%, including NSCLC (cORR 42.9% [N=14]; cORR 36.4% for EGFR mutant [N=11] and cORR 66.7% for EGFR wildtype [N=3]) and BC (cORR 100% [N=3]). Conclusions Iza-bren has demonstrated encouraging efficacy with an acceptable safety profile in multiple tumor types, including NSCLC and BC in this first report of a global population, consistent with the strong efficacy previously reported in Chinese pts. A global registrational study of first line TNBC is ongoing, while studies in other tumor types are planned.

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Title: Subtitle: 921MO Phase I global study of Iza-Bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and other solid tumors
Creators: H.A. Yu
X. Le
M.L. Johnson
N. Iannotti
A.I. Spira
P.A. Jänne
M. Furqan
T. Patil
G. Lopes
C.A. Perez
W.J. Edenfield
S.V. Liu
Z. Piotrowska
C. Park
J.L. Zhao
H. Wang
G. Russo
H. Zhu
J. Cheng
J. Peguero
Resource Type: Abstract
Publication Details: Annals of oncology, Vol.36(Suppl 2), pp.S601-S602
DOI: 10.1016/j.annonc.2025.08.1490
ISSN: 0923-7534
eISSN: 1569-8041
Publisher: Elsevier
Language: English
Date published: 09/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9985027354902771

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