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Anti-HER2 Bispecific Antibody ZW25 Activity in Combination With Chemotherapy With/Without Tislelizumab

Sponsor
BeiGene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04276493
Collaborator
(none)
80
Enrollment
22
Locations
2
Arms
86.1
Anticipated Duration (Months)
3.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the safety, tolerability and preliminary antitumor activity of ZW25 in combination with docetaxel in participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and ZW25 in combination with tislelizumab and chemotherapy in participants with HER2-positive gastric/gastroesophageal Junction (GEJ) adenocarcinoma

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
80 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 26, 2020
Actual Primary Completion Date :
Mar 29, 2022
Anticipated Study Completion Date :
May 31, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1- ZW25 + Docetaxel

ZW25 intravenous (IV) infusion followed by docetaxel IV infusion first-line therapy once every three weeks (Q3W) in female participants with metastatic breast cancer

Biological: ZW25
Administered as specified in the treatment arm

Drug: Docetaxel
Administered as specified in the treatment arm
Experimental: Cohort 2- ZW25 + Tiselizumab + Chemotherapy

ZW25 intravenous (IV) infusion followed by tiselizumab IV infusion and CAPOX chemotherapy (oral capecitabine + IV oxaliplatin) first-line therapy once every three weeks (Q3W) in participants with metastatic gastric / GEJ adenocarcinoma

Biological: ZW25
Administered as specified in the treatment arm

Biological: Tislelizumab
Administered as specified in the treatment arm
Other Names:
  • BGB-A317

    • Drug: Capecitabine
    Administered as specified in the treatment arm

    Drug: Oxaliplatin
    Administered as specified in the treatment arm

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants experiencing Adverse Events (AEs) [Up to 12 months after the last dose of study drug.]

    2. Number of Participants experiencing Severe Adverse Events (SAEs) as assessed by the investigator. [Up to 12 months after the last dose of study drug.]

    3. Objective response rate (ORR) [Up to 12 months after the last dose of study drug or before the initiation of a new anticancer treatment, whichever occurs first.]

      Defined as the proportion 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.

    Secondary Outcome Measures

    1. Duration of response (DOR) [Up to 36 Months]

    2. Time to response (TRR) [Up to 36 Months]

      Time from the start date of study drug to the first determination of an objective response by investigator per RECIST Version 1.1

    3. Progression-free survival (PFS) [Up to 36 Months]

      Proportion of participants with best overall response of complete response, partial response, and stable disease by investigator per RECIST Version 1.1

    4. Overall survival (OS) [Up to 60 Months]

      Time from the start date of study drug to the date of death due to any cause

    5. Serum concentration of ZW25 as a function of time [Predose and immediately postdose]

    6. Observed maximum plasma concentration during a sample interval (Cmax (ng/mL) [Predose and immediately postdose]

    7. Observed time to maximum plasma concentration during a sampling interval (tmax(hour)) [Predose and immediately postdose]

    8. Terminal elimination half-life (t1/2(hour)) [Predose and immediately postdose]

    9. Area under the plasma concentration-time curve from time zero to the last measurable timepoint (AUC(0-t) (ng*h/mL)) [Predose and immediately postdose]

    10. Apparent clearance after oral administration (CL/F(L/hr)) [Predose and immediately postdose]

    11. Presence of anti-ZW25-antibodies [Predose and immediately postdose]

    12. Presence of ZW25 neutralizing antibodies [Predose and immediately postdose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    1. Disease diagnosis and prior treatment:

    2. 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.

    1. 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

    1. At least 1 measurable lesion as defined per RECIST Version 1.1

    2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1

    3. Adequate organ function as indicated by the following laboratory values during screening:

    4. 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

    Key Exclusion Criteria:

    1. 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

    2. History of approved or investigative tyrosine kinase/HER inhibitors in any treatment setting

    1. except trastuzumab with or without pertuzumab used in neoadjuvant or adjuvant setting for Cohort 1

    1. Active leptomeningeal disease, untreated or uncontrolled brain metastasis

    2. 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 or breast)

    3. 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:

    1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)

    2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption

    3. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The fifth Medical Center, Chinese PLA General Hospital Beijing Beijing China 100071
    2 Beijing Cancer Hospital Beijing Beijing China 100142
    3 Guangdong Provincial People's Hospital Guangzhou Guangdong China 510080
    4 Jilin Cancer Hospital Changchun Jilin China 130012
    5 Liaoning Cancer Hospital & Institute - Medical Oncology - Oncology Shenyang Liaoning China 110017
    6 Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
    7 Chongqing Cancer Hospital Chongqing China 400030
    8 The Third Hospital of Nanchang Nanchang China 330025
    9 National Cancer Center Goyang-si Korea, Republic of 10408
    10 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13620
    11 Seoul National University Hospital Seoul Korea, Republic of 3080
    12 Severance Hospital, Yonsei University Seoul Korea, Republic of 3722
    13 Asan Medical Center Seoul Korea, Republic of 5505
    14 Gangnam Severance Hospital, Yonsei University Seoul Korea, Republic of 6273
    15 Samsung Medical Center Seoul Korea, Republic of 6351
    16 Seoul Saint Mary's Hospital Seoul Korea, Republic of 6591
    17 Korea University Guro Hospital Seoul Korea, Republic of
    18 Chang Gung Memorial Hospital, Kaohsiung Kaohsiung Taiwan 833
    19 China Medical University Hospital Taichung Taiwan 40447
    20 National Cheng Kung University Hospital Tainan Taiwan 704
    21 National Taiwan University Hospital Taipei Taiwan 100
    22 Taipei Veterans General Hospital Taipei Taiwan 11217

    Sponsors and Collaborators

    • BeiGene

    Investigators

    • Study Director: Vivian Li, MD, BeiGene

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    BeiGene
    ClinicalTrials.gov Identifier:
    NCT04276493
    Other Study ID Numbers:
    • BGB-A317-ZW25-101
    First Posted:
    Feb 19, 2020
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    Breast Neoplasms
    Docetaxel
    Capecitabine
    Oxaliplatin

    Study Results

    No Results Posted as of Apr 4, 2022