Clinical trial NCT04276493: Anti-HER2 Bispecific Antibody Zanidatamab (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Gastric Cancer
Gastroesophageal Junction Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2020-02-19
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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
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)
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.

Primary outcomes:
measure: Number of Participants experiencing Adverse Events (AEs)
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 41 months
measure: Number of Participants experiencing Serious Adverse Events (SAEs) as assessed by the investigator.
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 41 months
measure: Objective response rate (ORR)
timeFrame: 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:
measure: Duration of response (DOR)
timeFrame: From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 41 months
measure: Time to response (TTR)
timeFrame: From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 41 months
measure: Progression-free survival (PFS)
timeFrame: From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 41 months
measure: Overall survival (OS)
timeFrame: From the start date of study treatment to the documented death date or the last known alive date, up to approximately 41 months
measure: Serum concentration of zanidatamab as a function of time
timeFrame: Predose and immediately postdose
measure: Observed maximum plasma concentration of zanidatamab during a sample interval (Cmax)
timeFrame: Predose and immediately postdose
measure: Observed time to maximum plasma concentration of zanidatamab during a sampling interval (tmax)
timeFrame: Predose and immediately postdose
measure: Terminal elimination half-life (t1/2) of zanidatamab
timeFrame: Predose and immediately postdose
measure: Area under the plasma concentration-time curve from time zero to the last measurable timepoint (AUC(0-t)) of zanidatamab
timeFrame: Predose and immediately postdose
measure: Apparent clearance after oral administration (CL/F) of zanidatamab
timeFrame: Predose and immediately postdose
measure: Presence of anti-zanidatamab-antibodies
timeFrame: Predose and immediately postdose
measure: Presence of zanidatamab neutralizing antibodies
timeFrame: Predose and immediately postdose
measure: Number of participants with AEs and SAEs who entered the long-term extension period
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 51 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Affiliated Hospital of Military Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital Huifu Branch
state: Guangdong
city: Nanchang
country: China
facility: The Third Hospital of Nanchang
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Goyangsi
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnamsi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul Teugbyeolsi
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital East Campus
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: