Clinical Trials /

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

NCT04276493

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Anti-HER2 Bispecific Antibody ZW25 Activity in Combination With Chemotherapy With/Without Tislelizumab
  • 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

Clinical Trial IDs

  • ORG STUDY ID: BGB-A317-ZW25-101
  • NCT ID: NCT04276493

Conditions

  • Breast Cancer
  • Gastric Cancer
  • Gastroesophageal Junction Cancer

Interventions

DrugSynonymsArms
ZW25Cohort 1- ZW25 + Docetaxel
DocetaxelCohort 1- ZW25 + Docetaxel
TislelizumabBGB-A317Cohort 2- ZW25 + Tiselizumab + Chemotherapy
CapecitabineCohort 2- ZW25 + Tiselizumab + Chemotherapy
OxaliplatinCohort 2- ZW25 + Tiselizumab + Chemotherapy

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Cohort 1- ZW25 + DocetaxelExperimentalZW25 intravenous (IV) infusion followed by docetaxel IV infusion first-line therapy once every three weeks (Q3W) in female participants with metastatic breast cancer
  • ZW25
  • Docetaxel
Cohort 2- ZW25 + Tiselizumab + ChemotherapyExperimentalZW25 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
  • ZW25
  • Tislelizumab
  • Capecitabine
  • Oxaliplatin

Eligibility 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 or uncontrolled brain metastasis. Participants with
             equivocal findings or with confirmed brain metastases are eligible for enrollment
             provided that they are asymptomatic and radiologically stable without the need for
             corticosteroid treatment for ≥ 4 weeks before the first dose of study drug

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants experiencing Adverse Events (AEs)
Time Frame:Up to 12 months after the last dose of study drug.
Safety Issue:
Description: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

Measure:Duration of response (DOR)
Time Frame:Up to 36 Months
Safety Issue:
Description:
Measure:Time to response (TRR)
Time Frame:Up to 36 Months
Safety Issue:
Description:Time from the start date of study drug to the first determination of an objective response by investigator per RECIST Version 1.1
Measure:Progression-free survival (PFS)
Time Frame:Up to 36 Months
Safety Issue:
Description:Proportion of participants with best overall response of complete response, partial response, and stable disease by investigator per RECIST Version 1.1
Measure:Overall survival (OS)
Time Frame:Up to 60 Months
Safety Issue:
Description:Time from the start date of study drug to the date of death due to any cause
Measure:Serum concentration of ZW25 as a function of time
Time Frame:Predose and immediately postdose
Safety Issue:
Description:
Measure:Observed maximum plasma concentration during a sample interval (Cmax (ng/mL)
Time Frame:Predose and immediately postdose
Safety Issue:
Description:
Measure:Observed time to maximum plasma concentration during a sampling interval (tmax(hour))
Time Frame:Predose and immediately postdose
Safety Issue:
Description:
Measure:Terminal elimination half-life (t1/2(hour))
Time Frame:Predose and immediately postdose
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Apparent clearance after oral administration (CL/F(L/hr))
Time Frame:Predose and immediately postdose
Safety Issue:
Description:
Measure:Presence of anti-ZW25-antibodies
Time Frame:Predose and immediately postdose
Safety Issue:
Description:
Measure:Presence of ZW25 neutralizing antibodies
Time Frame:Predose and immediately postdose
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:BeiGene

Last Updated

February 18, 2020