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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Gastric Cancer; Gastroesophageal Junction Cancer
• Intervention / Treatment: Biological: ZW25; Drug: Docetaxel; Biological: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing, China, 400030
    • Chongqing Cancer Hospital
  • Nanchang, China, 330025
    • The Third Hospital of Nanchang
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100071
      • the Fifth Medical Center, Chinese PLA General Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110017
      • Liaoning Cancer Hospital & Institute - Medical Oncology - Oncology
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital, Yonsei University
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 6273
    • Gangnam Severance Hospital, Yonsei University
  • Seoul, Korea, Republic of, 6591
    • Seoul Saint Mary's Hospital
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Chang Gung Memorial Hospital, Kaohsiung
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: BGB-A317; Drug: Capecitabine; Administered as specified in the treatment arm; Drug: Oxaliplatin; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants experiencing Adverse Events (AEs)		Up to 12 months after the last dose of study drug.
Number of Participants experiencing Severe Adverse Events (SAEs) as assessed by the investigator.		Up to 12 months after the last dose of study drug.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)		Up to 36 Months
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
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
Overall survival (OS)	Time from the start date of study drug to the date of death due to any cause	Up to 60 Months
Serum concentration of ZW25 as a function of time		Predose and immediately postdose
Observed maximum plasma concentration during a sample interval (Cmax (ng/mL)		Predose and immediately postdose
Observed time to maximum plasma concentration during a sampling interval (tmax(hour))		Predose and immediately postdose
Terminal elimination half-life (t1/2(hour))		Predose and immediately postdose
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
Apparent clearance after oral administration (CL/F(L/hr))		Predose and immediately postdose
Presence of anti-ZW25-antibodies		Predose and immediately postdose
Presence of ZW25 neutralizing antibodies		Predose and immediately postdose

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2020
• Primary Completion (Actual): December 7, 2023
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Capecitabine; Oxaliplatin; Tislelizumab
• Other Study ID Numbers: BGB-A317-ZW25-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• 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