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

Breast Cancer Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04276493
• Other study ID #: BGB-A317-ZW25-101
• Secondary ID: CTR20210237
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 26, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 71
• Est. completion date: December 31, 2026
• Est. primary completion date: December 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Gastric Cancer
• Gastroesophageal Junction Cancer

Intervention

Biological:
• ZW25
Administered as specified in the treatment arm

Drug:
• Docetaxel
Administered as specified in the treatment arm

Biological:
• Tislelizumab
Administered as specified in the treatment arm

Drug:
• Capecitabine
Administered as specified in the treatment arm
• Oxaliplatin
Administered as specified in the treatment arm

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	The fifth Medical Center, Chinese PLA General Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Chongqing Cancer Hospital	Chongqing
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	The Third Hospital of Nanchang	Nanchang
China	Liaoning Cancer Hospital & Institute - Medical Oncology - Oncology	Shenyang	Liaoning
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital, Yonsei University	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul Saint Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Taiwan	Chang Gung Memorial Hospital, Kaohsiung	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

China,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants experiencing Adverse Events (AEs)		Up to 12 months after the last dose of study drug.
Primary	Number of Participants experiencing Severe Adverse Events (SAEs) as assessed by the investigator.		Up to 12 months after the last dose of study drug.
Primary	Objective response rate (ORR)	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.	Up to 12 months after the last dose of study drug or before the initiation of a new anticancer treatment, whichever occurs first.
Secondary	Duration of response (DOR)		Up to 36 Months
Secondary	Time to response (TRR)	Time from the start date of study drug to the first determination of an objective response by investigator per RECIST Version 1.1	Up to 36 Months
Secondary	Progression-free survival (PFS)	Proportion of participants with best overall response of complete response, partial response, and stable disease by investigator per RECIST Version 1.1	Up to 36 Months
Secondary	Overall survival (OS)	Time from the start date of study drug to the date of death due to any cause	Up to 60 Months
Secondary	Serum concentration of ZW25 as a function of time		Predose and immediately postdose
Secondary	Observed maximum plasma concentration during a sample interval (Cmax (ng/mL)		Predose and immediately postdose
Secondary	Observed time to maximum plasma concentration during a sampling interval (tmax(hour))		Predose and immediately postdose
Secondary	Terminal elimination half-life (t1/2(hour))		Predose and immediately postdose
Secondary	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
Secondary	Apparent clearance after oral administration (CL/F(L/hr))		Predose and immediately postdose
Secondary	Presence of anti-ZW25-antibodies		Predose and immediately postdose
Secondary	Presence of ZW25 neutralizing antibodies		Predose and immediately postdose