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
Overview
- Phase
- Phase 1
- Intervention
- Zanidatamab
- Conditions
- Breast Cancer
- Sponsor
- BeiGene
- Enrollment
- 71
- Locations
- 21
- Primary Endpoint
- Number of Participants experiencing Adverse Events (AEs)
- Status
- Completed
- Last Updated
- last year
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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)
Arms & Interventions
Cohort 1- Zanidatamab + Docetaxel
Zanidatamab intravenous (IV) infusion followed by docetaxel IV infusion first-line therapy once every three weeks (Q3W) in female participants with metastatic breast cancer
Intervention: Zanidatamab
Cohort 1- Zanidatamab + Docetaxel
Zanidatamab intravenous (IV) infusion followed by docetaxel IV infusion first-line therapy once every three weeks (Q3W) in female participants with metastatic breast cancer
Intervention: Docetaxel
Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy
Zanidatamab intravenous (IV) infusion followed by tislelizumab IV infusion and CAPOX chemotherapy (oral capecitabine + IV oxaliplatin) first-line therapy once every three weeks (Q3W) in participants with metastatic gastric / GEJ adenocarcinoma
Intervention: Zanidatamab
Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy
Zanidatamab intravenous (IV) infusion followed by tislelizumab IV infusion and CAPOX chemotherapy (oral capecitabine + IV oxaliplatin) first-line therapy once every three weeks (Q3W) in participants with metastatic gastric / GEJ adenocarcinoma
Intervention: Tislelizumab
Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy
Zanidatamab intravenous (IV) infusion followed by tislelizumab IV infusion and CAPOX chemotherapy (oral capecitabine + IV oxaliplatin) first-line therapy once every three weeks (Q3W) in participants with metastatic gastric / GEJ adenocarcinoma
Intervention: Capecitabine
Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy
Zanidatamab intravenous (IV) infusion followed by tislelizumab IV infusion and CAPOX chemotherapy (oral capecitabine + IV oxaliplatin) first-line therapy once every three weeks (Q3W) in participants with metastatic gastric / GEJ adenocarcinoma
Intervention: Oxaliplatin
Outcomes
Primary Outcomes
Number of Participants experiencing Adverse Events (AEs)
Time Frame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 41 months
Number of Participants experiencing Serious Adverse Events (SAEs) as assessed by the investigator.
Time Frame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 41 months
Objective response rate (ORR)
Time Frame: From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 41 months
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.
Secondary Outcomes
- 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 41 months)
- Time to response (TTR)(From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 41 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 41 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)
- Serum concentration of zanidatamab as a function of time(Predose and immediately postdose)
- Observed maximum plasma concentration of zanidatamab during a sample interval (Cmax)(Predose and immediately postdose)
- Observed time to maximum plasma concentration of zanidatamab during a sampling interval (tmax)(Predose and immediately postdose)
- Terminal elimination half-life (t1/2) of zanidatamab(Predose and immediately postdose)
- Area under the plasma concentration-time curve from time zero to the last measurable timepoint (AUC(0-t)) of zanidatamab(Predose and immediately postdose)
- Apparent clearance after oral administration (CL/F) of zanidatamab(Predose and immediately postdose)
- Presence of anti-zanidatamab-antibodies(Predose and immediately postdose)
- Presence of zanidatamab neutralizing antibodies(Predose and immediately postdose)
- Number of participants with AEs and SAEs who entered the long-term extension period(From the first dose of study drug(s) to 30 days after the last dose; up to approximately 51 months)