Meeting
2023 ASCO Breakthrough
Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line therapy (1L) for patients (pts) with advanced HER2-positive breast cancer (BC): Updated results from a phase Ib/II study.
Authors
Xiaojia Wang
Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China
Xiaojia Wang , Keun Seok Lee , Xiaohua Zeng , Tao Sun , Young-Hyuck Im , Huiping Li , Kun Wang , Huiyan Li , Ping Zhou , Yuanyuan Bao , Zefei Jiang
Organizations
Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China, Department of Oncology, National Cancer Center, Goyang-Si, South Korea, Department of Breast Oncology, Chongqing University Cancer Hospital, Chongqing, China, Department of Breast Oncology, Liaoning Cancer Hospital, Liaoning, China, Department of Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Department of Breast Oncology, Beijing Cancer Hospital, Beijing, China, Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China, Clinical Development, BeiGene (Shanghai) Co., Ltd., Shanghai, China, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
Research Funding
Pharmaceutical/Biotech Company
BeiGene, Ltd., This study was sponsored by BeiGene, Ltd. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Emily Finn, MSc, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.
Background: Despite HER2-targeted agents improving outcomes in HER2-positive (+) BC, some pts develop resistance, relapse, or do not respond to current 1L therapies. Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2. Preliminary results from this Phase Ib/II trial (NCT04276493) showed that zani plus docetaxel had a manageable safety profile and demonstrated promising antitumor activity in pts with advanced HER2+ BC; here we present the updated data following enrollment completion. Methods: Cohort 1 of this open-label study is evaluating zani in combination with docetaxel as a 1L therapy in adult females with advanced HER2+ BC who may have received prior neoadjuvant/adjuvant therapy. Cohort 1a pts received zani 30 mg/kg intravenously (IV), Cohort 1b pts received zani 1800 mg IV, both with docetaxel 75 mg/m2 IV every 3 weeks. The primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR) and disease control rate (DCR). Results: As of Nov 22, 2022, 37 pts(median age 55.0 years [range: 33-80]) were assigned to Cohort 1a (n=10) or 1b (n=27). Median study follow-up was 15.5 months (range: 1.1-29.3); patients received a median of 13 treatment cycles (range 1-37) and 18 (48.6%) pts remained on treatment. Of the 33-efficacy evaluable (EE) pts, confirmed ORR was 90.9% (95% confidence interval [CI]: 75.7, 98.1). Efficacy data are summarized in the table. In total, 36 (97.3%) pts experienced ≥1 treatment-related adverse event (TRAE); 25 (67.6%) pts experienced ≥grade 3 TRAEs. The most common ≥grade 3 TRAEs were decreased neutrophil count, experienced by 18 (48.6%) pts, and decreased white blood cell count, experienced by 7 (18.9%) pts. Serious TRAEs occurred in 6 (16.2%) pts; no TRAEs led to death. Conclusions: Zani combined with docetaxel demonstrated promising antitumor activity as 1L therapy for advanced HER2+ BC, with a manageable safety profile. Clinical trial information: NCT04276493.
| Cohort 1a (n=8) | Cohort 1b (n=25) | Total (n=33) | |
|---|---|---|---|
| Confirmed best overall response, n (%) | |||
| Complete response | 1 (12.5) | 1 (4.0) | 2 (6.1) |
| Partial response | 7 (87.5) | 21 (84.0) | 28 (84.8) |
| Stable disease | 0 (0.0) | 2 (8.0) | 2 (6.1) |
| Progressive disease | 0 (0.0) | 1 (4.0) | 1 (3.0) |
| Confirmed ORR, n (%) 95% CI | 8 (100) 63.1, 100 | 22 (88.0) 68.8, 97.5 | 30 (90.9) 75.7, 98.1 |
| Confirmed DCR, n (%) 95% CI | 8 (100) 63.1, 100 | 24 (96.0) 79.6, 99.9 | 32 (97.0) 84.2, 99.9 |
| Median DoR, months (95% CI) | 12.4 5.5, NE | NE 12.1, NE | NE 12.1, NE |
| Confirmed DoR, range† | 3.5†-23.5† | 4.3†-16.5† | 3.5†-23.5† |
*Four pts without any postbaseline tumor assessments were excluded from the EE analysis set.
Data cut off: November 22, 2022.
†Censored.
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Abstract Details
Session Type
Rapid Oral Abstract Session
Session Title
Rapid Abstract Session A: Trials and Experimental Therapeutics
Track
Breast Cancer,Central Nervous System Tumors,Developmental Therapeutics,Genitourinary Cancer,Gynecologic Cancer,Head and Neck Cancer,Gastrointestinal Cancer,Hematologic Malignancies,Quality of Care,Genetics/Genomics/Multiomics,Healthcare Equity and Access to Care,Healthtech Innovations,Models of Care and Care Delivery,Population Health,Thoracic Cancers,Viral-Mediated Malignancies,Other Malignancies or Topics
Sub Track
Targeted Therapies
Clinical Trial Registration Number
NCT04276493
Citation
JCO Global Oncology 9, 2023 (suppl 1; abstr 1)
DOI
10.1200/GO.2023.9.Supplement_1.1
Abstract #
1
Abstract Disclosures
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