Health Condition 1: C16- Malignant neoplasm of stomach
Conditions
Interventions
Intervention1: Zanidatamab: Humanized, bispecific, immunoglobulin G isotype 1 (IgG1)-like antibody.
Subject participation in this study will be up to 32 days.
Administered intravenously on Day 1 of ea
Sponsors
Zymeworks Inc
PPD Pharmaceutical Development India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1.Histologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment. 2.New formalin-fixed, paraffin-embedded tumor (FFPE) sample or archival tumor tissues must be tested at a central laboratory to confirm HER2 status prior to randomization 3.Assessable (measurable or non-measurable) disease as defined by RECIST 1.1 4.Male or female, = 18 years of age (or the legal age of adulthood per country-specific regulations). 5.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization 6.Adequate hepatic function, as defined by both: a.Aspartate aminotransferase (AST) = 2.5 × upper limit of normal (ULN), and alanine aminotransferase (ALT) = 2.5 × ULN. For subjects with liver involvement, AST and ALT = 5.0 × ULN is acceptable. b.Total bilirubin = 1.5 × the ULN or = 2.5 × ULN for subjects with Gilbert’s disease 7.Adequate renal function, as defined by estimated glomerular filtration rate (GFR) > 50 mL/min per local institutional standard method 8.Hematologic function as follows: a. Absolute neutrophil count (ANC) = 1.5 × 109 /L. For the EU and United Kingdom, ANC must be = 2.0 × 109 /L. b. Platelet count = 100 × 109 /L c. Hemoglobin = 8 g/dL. Subjects with chronic anemia that is supported by intermittent red blood cell (RBC) transfusions are eligible 9.Left ventricular ejection fraction (LVEF) = 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA) 10.Female subjects of childbearing potential must have a negative serum/plasma or urine beta human chorionic gonadotropin (ß-hCG) pregnancy test result within 3 days prior to randomization. Females with false positive urine test results can be enrolled if subsequent serum/plasma testing is negative 11.Female subjects of childbearing potential and male subjects with a partner of childbearing potential must be willing to use 2 methods of birth control with a failure rate of less than 1% per year during the study and for at least 14 months after the last dose of cisplatin, at least 9 months after the last dose of oxaliplatin, and at least 7 months after the last dose for all other study drugs. These include, but are not limited to, established use of oral, implanted, or injected hormonal contraceptives or placement of intra-uterine device or intra-uterine system 12.Male subjects must agree to use condoms and not to donate sperm, and female subjects must agree not to donate oocytes starting at screening and throughout the study period, and for at least 14 months after the last dose of cisplatin, at least 9 months after the last dose of oxaliplatin, and at least 7 months after the last dose for all other study drugs 13.The subject or subject’s legally acceptable representative must provide written informed consent. Subjects who elect to be pre-screened for HER2 status must provide a separate written informed consent for collection, storage, and analysis of the tumor tissue.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with a HER2-targeted agent, with the exception of subjects who received HER2-targeted treatment for breast cancer > 5 years prior to initial diagnosis of GEA 2. Prior treatment 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 3. Prior treatment with systemic antineoplastic therapy for unresectable locally advanced, recurrent or metastatic GEA. Subjects who have received treatment with adjuvant or neoadjuvant chemotherapy or chemoradiotherapy must not have cancer recurrence or progression within 6 months of completing that therapy. Subjects who have received prior palliative local therapy (e.g., radiation therapy) are eligible. 4. Received radiation therapy within 14 days prior to randomization 5. Total lifetime anthracycline load exceeding 360 mg/m2 doxorubicin or equivalent 6. Any condition that requires systemic treatment with either corticosteroids ( > 10 mg daily of prednisone or equivalent) or other immunosuppressive medication = 14 days prior to randomization. Note: Subjects who are currently or have previously been on any of the following steroid regimens are not excluded: a. Adrenal replacement steroid (dose = 10 mg daily of prednisone or equivalent) b. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption c. Short course (= 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen) 7. History of hypersensitivity or contraindications to any active substance/active ingredient of any study medication, including chemotherapy components (cisplatin, oxaliplatin, 5-fluorouracil, or capecitabine), murine proteins (trastuzumab), monoclonal antibodies, recombinant proteins, and/or any of the excipients listed in the ingredients of any drug formulation 8. Known dihydropyrimidine dehydrogenase (DPD) deficiency or use of any medications known to inhibit DPD (including brivudine, sorivudine and analogs) within 4 weeks prior to randomization 9. Major surgery within 28 days prior to randomization 10. The following disease-related risk factors: a. Clinically significant bleeding (Common Toxicity Criteria for Adverse Events [CTCAE] = Grade 3) from the gastrointestinal (GI) tract within 4 weeks prior to randomization b. Clinically significant bowel obstruction (CTCAE = Grade 3) c. Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to randomization. Receipt of diuretic drugs for other reasons is acceptable. 11. Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks prior to randomization. Stable, treated brain metastases are allowed (defined as subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization). 12. Known history of or ongoing leptomeningeal disease (LMD). Subjects will be eligible if LMD has been reported radiographically but is not suspected clinically by the investigator and the subject does not have neurological symptoms of LMD. 13. Poorly controlled sei
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Progression-free survival (PFS) by blinded independent central review (BICR). 2. Overall survivalTimepoint: 1. The time from randomization to the date of documented disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) as assessed by BICR or death from any cause, up to 2.5 years. 2. The time from randomization to death due to any cause, up to 3.5 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Confirmed objective response rate (ORR) by BICR.Timepoint: The time from randomization to best overall response of complete response or partial response, up to 2.5 yrs.;Duration of response by BICRTimepoint: The time from first objective response (CR or PR) to documented progressive disease or death from any cause, up to 2.5 years.;Duration of response per Investigator AssessmentTimepoint: The time from first objective response (CR or PR) to documented progressive disease or death from any cause, up to 2.5 years.;Health-related quality of life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (core cancer questionnaire) C30 (QLQ-C30).Timepoint: Changes from baseline in the EORTC QLQ-C30 scores, up to 2.5 years.;HRQoL as assessed by EORTC Quality of Life Questionnaire OG25 module (QLQ-OG25)Timepoint: Changes from baseline in the EORTC QLQ-OG25 scores, up to 2.5 years.;HRQol as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire.Timepoint: Changes from baseline in the EORTC EQ-5D-5L questionnaire scores, up to 2.5 years.;Incidence of adverse eventsTimepoint: Number of subjects who experienced adverse events or serious adverse events, up to 2 years.;Incidence of anti-drug antibodies (ADAs)Timepoint: Number of patients who develop ADAs, up to 2 years;Incidence of clinical laboratory abnormalitiesTimepoint: Number of patients who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, up to 2 years;ORR per Investigator AssessmentTimepoint: Number of patients who achieved a best overall response of CR or PR as determined per RECIST 1.1 as assessed by Investigator, up to 2.5 years.;PFS per Investigator AssessmentTimepoint: The time from randomization to the date of documented disease prog | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Czech Republic, Estonia, France, Georgia, Germany, Greece, Guatemala, India, Ireland, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Poland, Portugal, Republic of Korea, Romania, Russian Federation, Serbia, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United States of America
Contacts
Public ContactRashmi Chitgupi
PPD Pharmaceutical Development India Private Limited
Outcome results
None listed