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Trial record 1 of 1 for:    NCT04276493
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Anti-HER2 Bispecific Antibody ZW25 Activity in Combination With Chemotherapy With/Without Tislelizumab

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ClinicalTrials.gov Identifier: NCT04276493
Recruitment Status : Active, not recruiting
First Posted : February 19, 2020
Last Update Posted : February 9, 2023
Sponsor:
Information provided by (Responsible Party):
BeiGene

Study Description
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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
Breast Cancer Gastric Cancer Gastroesophageal Junction Cancer Biological: ZW25 Drug: Docetaxel Biological: Tislelizumab Drug: Capecitabine Drug: Oxaliplatin Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 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 : March 26, 2020
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: BGB-A317

Drug: Capecitabine
Administered as specified in the treatment arm

Drug: Oxaliplatin
Administered as specified in the treatment arm


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants experiencing Adverse Events (AEs) [ Time Frame: 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. [ Time Frame: Up to 12 months after the last dose of study drug. ]
  3. Objective response rate (ORR) [ Time Frame: 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) [ Time Frame: Up to 36 Months ]
  2. Time to response (TRR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Predose and immediately postdose ]
  6. Observed maximum plasma concentration during a sample interval (Cmax (ng/mL) [ Time Frame: Predose and immediately postdose ]
  7. Observed time to maximum plasma concentration during a sampling interval (tmax(hour)) [ Time Frame: Predose and immediately postdose ]
  8. Terminal elimination half-life (t1/2(hour)) [ Time Frame: 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)) [ Time Frame: Predose and immediately postdose ]
  10. Apparent clearance after oral administration (CL/F(L/hr)) [ Time Frame: Predose and immediately postdose ]
  11. Presence of anti-ZW25-antibodies [ Time Frame: Predose and immediately postdose ]
  12. Presence of ZW25 neutralizing antibodies [ Time Frame: Predose and immediately postdose ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Disease diagnosis and prior treatment:

    1. 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.

    2. 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
  2. At least 1 measurable lesion as defined per RECIST Version 1.1
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
  4. Adequate organ function as indicated by the following laboratory values during screening:
  5. 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

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

  3. Active leptomeningeal disease, untreated or uncontrolled brain metastasis
  4. 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)
  5. 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04276493


Locations
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Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Study Director BeiGene
More Information
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT04276493    
Other Study ID Numbers: BGB-A317-ZW25-101
First Posted: February 19, 2020    Key Record Dates
Last Update Posted: February 9, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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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:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Capecitabine
Oxaliplatin
Tislelizumab
 Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological