Breast Cancer, Gastric Cancer, Gastroesophageal Junction Cancer
Conditions
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
Interventions
BIOLOGICALZanidatamab
Administered intravenously
DRUGDocetaxel
Administered intravenously
BIOLOGICALTislelizumab
Administered intravenously
DRUGCapecitabine
Administered orally
DRUGOxaliplatin
Administered intravenously
Sponsors
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatments, whether considered related to study treatments or not. A serious AE (SAE) was any untoward medical occurrence that, at any dose - resulted in death, - was life threatening, - required hospitalization or prolongation of existing hospitalization, - resulted in disability/incapacity, - was a congenital anomaly/birth defect. |
| Objective Response Rate (ORR) | Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42months. | ORR is 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. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Timepoint (AUC(0-t)) of Zanidatamab | Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days. | — |
| Observed Maximum Plasma Concentration of Zanidatamab During a Sample Interval (Cmax) | Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days. | — |
| Observed Time to Maximum Plasma Concentration of Zanidatamab During a Sampling Interval (Tmax) | Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days. | — |
| Terminal Elimination Half-life (t1/2) of Zanidatamab | Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days. | — |
| Apparent Clearance After Oral Administration (CL/F) of Zanidatamab | Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose | — |
| Number of Participants With Anti-zanidatamab Antibodies | From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months | — |
| Number of Participants With AEs and SAEs in Participants 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 | — |
| 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 42 months | DOR is defined as the time from the first determination of an objective response until the first documentation of disease progression or death, whichever occurred first. |
| Time to Response (TTR) | From the start date of study treatment to the first documentation of response, whichever occurs first, up to approximately 42 months | Time to response is defined as the time from the start date of study treatment to the first determination of an objective response assessed by investigator per RECIST v 1.1. |
| 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 42 months | PFS is defined as the time from the start date of study drug to the date of the first objectively documented tumor progression assessed by investigator per RECIST Version 1.1 or death, whichever occurred first. |
| 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 | Time from the start date of study drug to the date of death due to any cause. |
| Disease Control Rate (DCR) | Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42 months. | DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR, and stable disease by investigator per RECIST Version 1.1. BOR is the best response recorded from the start of the study drug treatment until the end of treatment taking into account any requirement for confirmation. |
| Serum Concentration of Zanidatamab as a Function of Time | Day 1 end of infusion of Cycle 1, 2, 5, 9, 17, 26 and 35. Each cycle is 21 days | — |
Countries
China, South Korea, Taiwan
Contacts
STUDY_DIRECTORStudy Director
BeiGene
Participant flow
Recruitment details
The study was conducted at 22 study centers in China, Korea, and Taiwan; 22 centers enrolled a total of 71 participants.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 10.05 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 5 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 71 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 11 | 3 / 27 | 11 / 19 | 5 / 14 |
| other Total, other adverse events | 11 / 11 | 27 / 27 | 19 / 19 | 14 / 14 |
| serious Total, serious adverse events | 2 / 11 | 10 / 27 | 12 / 19 | 5 / 14 |
Outcome results
None listed