Breast CancerPhase 1/2NCT04276493
Anti-HER2 Bispecific Antibody Zanidatamab (ZW25) Activity in Combination With Chemotherapy With/Without Tislelizumab
A Phase 1/2 study testing Zanidatamab, Docetaxel and Tislelizumab in people with Breast Cancer and Gastric Cancer, run by BeiGene at 21 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Gastric Cancer, Gastroesophageal Junction Cancer
- What is being tested?
- Zanidatamab, Docetaxel and Tislelizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 21 sitesin 3 countries
- Study dates
- 23 Mar 2020to 31 Oct 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
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- 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
Who cannot join
- 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
- 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
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- 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)
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
21 sites in 3 countries.
21 sites in 3 countries
China8 sites
The Affiliated Hospital of Military Medical Sciences
Beijing, Beijing Municipality, 100071
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Jilin Cancer Hospital
Changchun, Jilin, 130021
Chongqing Cancer Hospital
Chongqing, Chongqing Municipality, 400030
Guangdong Provincial Peoples Hospital Huifu Branch
Guangzhou, Guangdong, 510120
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
The Third Hospital of Nanchang
Nanchang, Jiangxi, 330009
Liaoning Cancer Hospital and Institute
Shenyang, Liaoning, 110042
South Korea8 sites
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, 03080
Severance Hospital Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 03722
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 05505
Gangnam Severance Hospital, Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 06273
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, 06351
Korea University Guro Hospital
Seoul, Seoul Teugbyeolsi, 08308
Taiwan5 sites
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301
China Medical University Hospital
Taichung, 40447
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital East Campus
Taipei, 100225
Taipei Veterans General Hospital
Taipei, 11217
About this study
Official title: 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
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
- Being tested
- Zanidatamab, Docetaxel, Tislelizumab, Capecitabine, Oxaliplatin
- Medical subject headings
- Breast Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanidatamabBiological
Also called ZW25
Administered intravenously
DocetaxelDrug
Administered intravenously
TislelizumabBiological
Also called BGB-A317
Administered intravenously
CapecitabineDrug
Administered orally
OxaliplatinDrug
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A: Breast Cancer: Zanidatamab 30 mg/kg + Docetaxel | Experimental | Participants 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. Receives: Biological: Zanidatamab; Drug: Docetaxel |
| Cohort 1B: Breast Cancer: Zanidatamab 1800 mg + Docetaxel | Experimental | Participants 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. Receives: Biological: Zanidatamab; Drug: Docetaxel |
| Cohort 2A: Gastric/GEJC: Zanidatamab 30 mg/kg + Tislelizumab + CAPOX | Experimental | Participants 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. Receives: Biological: Zanidatamab; Biological: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin |
| Cohort 2B: Gastric/GEJC : Zanidatamab 1800/2400 mg + Tislelizumab + CAPOX | Experimental | Participants 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. Receives: Biological: Zanidatamab; Biological: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
DOR is defined as the time from the first determination of an objective response until the first documentation of disease progression or death, whichever occurred first.
Measured: 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)
Time to response is defined as the time from the start date of study treatment to the first determination of an objective response assessed by investigator per RECIST v 1.1.
Measured: 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)
PFS is defined as the time from the start date of study drug to the date of the first objectively documented tumor progression assessed by investigator per RECIST Version 1.1 or death, whichever occurred first.
Measured: 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)
DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR, and stable disease by investigator per RECIST Version 1.1.
BOR is the best response recorded from the start of the study drug treatment until the end of treatment taking into account any requirement for confirmation.
Measured: 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)
Time from the start date of study drug to the date of death due to any cause.
Measured: From the start date of study treatment to the documented death date or the last known alive date, up to approximately 41 months
Serum Concentration of Zanidatamab as a Function of Time
Measured: Day 1 end of infusion of Cycle 1, 2, 5, 9, 17, 26 and 35. Each cycle is 21 days
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Timepoint (AUC(0-t)) of Zanidatamab
Measured: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Observed Maximum Plasma Concentration of Zanidatamab During a Sample Interval (Cmax)
Measured: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Observed Time to Maximum Plasma Concentration of Zanidatamab During a Sampling Interval (Tmax)
Measured: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Terminal Elimination Half-life (t1/2) of Zanidatamab
Measured: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Apparent Clearance After Oral Administration (CL/F) of Zanidatamab
Measured: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose
Number of Participants With Anti-zanidatamab Antibodies
Measured: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months
Number of Participants With AEs and SAEs in Participants Who Entered the Long-term Extension Period
Measured: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 51 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start23 Mar 2020
- Primary completion7 Dec 2023
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276493
- Sponsor's protocol ID
- BGB-A317-ZW25-101
- Other IDs
- CTR20210237
- Status last verified
- Aug 2026
- First submitted
- 4 Feb 2020
- Last updated
- 2 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 41202501Lee 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.
PubMed 41324998