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

NCT04276493 | Completed Phase 1 FDA Drug

• 2 other identifiers: BGB-A317-ZW25-101CTR20210237
• Study Type: interventional
• Target: 71
• Locations: 3 countries
• Sites: 21

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

Conditions

Breast Cancer; Gastric Cancer; Gastroesophageal Junction Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants experiencing Adverse Events (AEs)

  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.

  From the first dose of study drug(s) to 30 days after the last dose; up to approximately 41 months

• Objective response rate (ORR)

  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.

  From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 41 months

Secondary Outcomes (13)

• 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

Study Arms (2)

Cohort 1- Zanidatamab + Docetaxel

EXPERIMENTAL

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

Biological: Zanidatamab; Drug: Docetaxel

Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy

EXPERIMENTAL

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

Biological: Zanidatamab; Biological: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin

Interventions

Zanidatamab BIOLOGICAL

Administered intravenously

Also known as: ZW25

Cohort 1- Zanidatamab + Docetaxel; Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy

Docetaxel DRUG

Administered intravenously

Cohort 1- Zanidatamab + Docetaxel

Tislelizumab BIOLOGICAL

Administered intravenously

Also known as: BGB-A317

Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy

Capecitabine DRUG

Administered orally

Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy

Oxaliplatin DRUG

Administered intravenously

Cohort 2- Zanidatamab + Tiselizumab + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
• Adequate organ function
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• BeiGene: lead

Study Sites (21)

The Affiliated Hospital of Military Medical Sciences

Beijing, Beijing Municipality, 100071, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

Location

Guangdong Provincial Peoples Hospital Huifu Branch

Guangzhou, Guangdong, 510120, China

Location

The Third Hospital of Nanchang

Nanchang, Jiangxi, 330009, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130021, China

Location

Liaoning Cancer Hospital and Institute

Shenyang, Liaoning, 110042, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 03722, South Korea

Location

Asan Medical Center

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 06273, South Korea

Location

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

Korea University Guro Hospital

Seoul, Seoul Teugbyeolsi, 08308, South Korea

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital East Campus

Taipei, 100225, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Breast Neoplasms; Stomach Neoplasms

Interventions

zanidatamab; Docetaxel; tislelizumab; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 19, 2020
• Study Start: March 26, 2020
• Primary Completion: December 7, 2023
• Study Completion: October 31, 2024
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (8); TW (5); KR (8)