Anti-HER2 Bispecific Antibody Zanidatamab (ZW25) Activity in Combination With Chemotherapy With/Without Tislelizumab
Phase 1b/2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-HER2 Bispecific Antibody ZW25 in Combination With Chemotherapy With/Without Tislelizumab in Patients With Advanced HER2-positive Breast Cancer or Gastric/Gastroesophageal Junction Adenocarcinoma
2 other identifiers
interventional
71
3 countries
21
Brief Summary
The purpose of the study is to assess the safety, tolerability and preliminary antitumor activity of zanidatamab in combination with docetaxel in participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and zanidatamab in combination with tislelizumab and chemotherapy in participants with HER2-positive gastric/gastroesophageal Junction (GEJ) adenocarcinoma
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 breast-cancer
Started Mar 2020
Typical duration for phase_1 breast-cancer
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2020
CompletedFirst Posted
Study publicly available on registry
February 19, 2020
CompletedStudy Start
First participant enrolled
March 23, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 7, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 31, 2024
CompletedResults Posted
Study results publicly available
September 2, 2026
CompletedSeptember 2, 2026
August 1, 2026
3.7 years
February 4, 2020
August 12, 2026
August 12, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatments, whether considered related to study treatments or not. A serious AE (SAE) was any untoward medical occurrence that, at any dose - resulted in death, - was life threatening, - required hospitalization or prolongation of existing hospitalization, - resulted in disability/incapacity, - was a congenital anomaly/birth defect.
From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who had a best overall response of complete response or partial response per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42months.
Secondary Outcomes (13)
Duration of Response (DOR)
From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 42 months
Time to Response (TTR)
From the start date of study treatment to the first documentation of response, whichever occurs first, up to approximately 42 months
Progression-free Survival (PFS)
From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 42 months
Disease Control Rate (DCR)
Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42 months.
Overall Survival (OS)
From the start date of study treatment to the documented death date or the last known alive date, up to approximately 41 months
- +8 more secondary outcomes
Study Arms (4)
Cohort 1A: Breast Cancer: Zanidatamab 30 mg/kg + Docetaxel
EXPERIMENTALParticipants with HER2+ breast cancer received zanidatamab 30 mg/kg intravenously (IV) and docetaxel 75 mg/m\^2 IV once every 3 weeks (Q3W) for an initial period of up to six cycles. After cycle 6, continuation of docetaxel treatment was at the discretion of the investigator. Zanidatamab was administered until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met.
Cohort 1B: Breast Cancer: Zanidatamab 1800 mg + Docetaxel
EXPERIMENTALParticipants with HER2+ breast cancer received zanidatamab 1800 mg/kg IV and docetaxel 75 mg/m\^2 IV Q3W for an initial period of up to six cycles. After cycle 6, continuation of docetaxel treatment was at the discretion of the investigator. Zanidatamab was administered until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met.
Cohort 2A: Gastric/GEJC: Zanidatamab 30 mg/kg + Tislelizumab + CAPOX
EXPERIMENTALParticipants with HER2+ gastric / gastroesophageal junction cancer (GEJC) received zanidatamab 30 mg/kg IV and tislelizumab 200 mg IV once every 3 weeks until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met. Participants also received CAPOX chemotherapy (1000 mg/m\^2 oral capecitabine twice daily for 14 days in each cycle and 130 mg/m\^2 oxaliplatin IV once every 3 weeks) for up to 6 six cycles. After cycle 6, oxaliplatin was discontinued and continuation of capecitabine as maintenance treatment was at the investigator's discretion.
Cohort 2B: Gastric/GEJC : Zanidatamab 1800/2400 mg + Tislelizumab + CAPOX
EXPERIMENTALParticipants with HER2+ gastric / GEJC received zanidatamab 1800 mg (participants with body weight \< 70 kg) or 2400 mg (participants with body weight ≥ 70 kg) IV and tislelizumab 200 mg IV Q3W until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met. Participants also received CAPOX chemotherapy (1000 mg/m\^2 oral capecitabine twice daily for 14 days in each cycle and 130 mg/m\^2 oxaliplatin IV once every 3 weeks) for up to 6 six cycles. After cycle 6, oxaliplatin was discontinued and continuation of capecitabine as maintenance treatment was at the investigator's discretion.
Interventions
Administered intravenously
Administered intravenously
Administered intravenously
Administered orally
Administered intravenously
Eligibility Criteria
You may qualify if:
- Disease diagnosis and prior treatment:
- Cohort 1 (the first-line breast cancer treatment cohort):
- Female participants with histologically or cytologically confirmed unresectable, locally advanced, recurrent or metastatic adenocarcinoma of the breast and candidate for chemotherapy. Locally recurrent disease must not be amenable to resection with curative intent.
- Human epidermal growth factor receptor 2 (HER2) IHC 3+ or in situ hybridization positive on the archival tumor tissue or fresh biopsy sample.
- Have not received previous systemic anticancer therapy for locally advanced unresectable or metastatic disease.
- Cohort 2 (the first-line gastric/gastroesophageal junction adenocarcinoma treatment cohort):
- Histologically or cytologically confirmed unresectable, locally advanced, recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction
- HER2 IHC 3+ or HER2 IHC 2+ together with in situ hybridization positive on the archival tumor tissue or fresh biopsy sample.
- Have not received previous systemic anticancer therapy for locally advanced unresectable or metastatic disease, including any approved or investigational estimated glomerular filtration rate (EGFR) or anti-HER2 agents or vaccines, cytotoxic chemotherapy or checkpoint inhibitors
- At least 1 measurable lesion as defined per RECIST Version 1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Adequate organ function
- Left ventricular ejection fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram or multigated acquisition scan (MUGA) (echocardiogram is the preferred method) within 28 days before the first dose of study drug
You may not qualify if:
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- History of approved or investigative tyrosine kinase/HER inhibitors in any treatment setting
- a. except trastuzumab with or without pertuzumab used in neoadjuvant or adjuvant setting for Cohort 1
- Active leptomeningeal disease, untreated or uncontrolled brain metastasis
- Any active malignancy ≤ 2 years before the first dose of study drug, except for the specific cancer under investigation in this trial and any localized cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix)
- Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug
- Note: Participants who are currently or have previously been on any of the following steroid regimens are not excluded:
- Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
- Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption
- Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BeiGenelead
Study Sites (21)
The Affiliated Hospital of Military Medical Sciences
Beijing, Beijing Municipality, 100071, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
Chongqing Cancer Hospital
Chongqing, Chongqing Municipality, 400030, China
Guangdong Provincial Peoples Hospital Huifu Branch
Guangzhou, Guangdong, 510120, China
The Third Hospital of Nanchang
Nanchang, Jiangxi, 330009, China
Jilin Cancer Hospital
Changchun, Jilin, 130021, China
Liaoning Cancer Hospital and Institute
Shenyang, Liaoning, 110042, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
National Cancer Center
Goyang-si, Gyeonggi-do, 10408, South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620, South Korea
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, 03080, South Korea
Severance Hospital Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 03722, South Korea
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 05505, South Korea
Gangnam Severance Hospital, Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 06273, South Korea
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, 06351, South Korea
Korea University Guro Hospital
Seoul, Seoul Teugbyeolsi, 08308, South Korea
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
National Cheng Kung University Hospital
Tainan, 704, Taiwan
National Taiwan University Hospital East Campus
Taipei, 100225, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Related Publications (2)
Wang X, Lee KS, Zeng X, Sun T, Im YH, Li H, Wang K, Zhou P, Li V, Chen S, Jiang Z. Zanidatamab in combination with docetaxel in first-line HER2-positive breast cancer: results from an open-label, multicenter, phase Ib/II study. ESMO Open. 2025 Nov;10(11):105852. doi: 10.1016/j.esmoop.2025.105852. Epub 2025 Nov 6.
PMID: 41202501RESULTLee KW, Bai LY, Jung M, Ying J, Im YH, Oh DY, Cho JY, Oh SC, Chao Y, Kim JW, Chen Y, Li V, Chen S, Kang YK. Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2026 Jan 16;32(2):312-323. doi: 10.1158/1078-0432.CCR-24-4295.
PMID: 41324998RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- BeiGene
Study Officials
- STUDY DIRECTOR
Study Director
BeiGene
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 4, 2020
First Posted
February 19, 2020
Study Start
March 23, 2020
Primary Completion
December 7, 2023
Study Completion
October 31, 2024
Last Updated
September 2, 2026
Results First Posted
September 2, 2026
Record last verified: 2026-08
Data Sharing
- IPD Sharing
- Will share