ZOLBETUXIMAB for Gastric adenocarcinoma|Gastroesophageal junction adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Participant is ≥ 18 years of age at the time of signing informed consent."}
• {"criterion_text":"- Participant’s tumor expresses PD-L1 CPS ≥1 as determined by central IHC testing. Participants with known microsatellite instability-high or mismatch repair deficient status may enroll as long as they meet the PD-L1 positivity criteria set forth in this protocol."}
• {"criterion_text":"- Participant has histologically confirmed gastric or gastroesophageal adenocarcinoma"}
• {"criterion_text":"- Participant has radiographically confirmed, locally advanced unresectable or metastatic disease within 28 days prior to randomization."}
• {"criterion_text":"- Participant has radiologically evaluable disease (measurable and/or nonmeasurable) according to RECIST V1.1, per investigator assessment, ≤ 28 days prior to randomization. For participants with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy."}
• {"criterion_text":"- Participant has Eastern Cooperataive Oncology Group performance status 0 to 1."}
• {"criterion_text":"- Participant has predicted life expectancy ≥ 12 weeks in the opinion of the investigator."}
• {"criterion_text":"- Participant must be a candidate to receive mFOLFOX6 or CAPOX and pembrolizumab."}
• {"criterion_text":"- Participant has a HER2-negative tumor."}
• {"criterion_text":"- Participant’s tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing."}

Exclusion criteria

• {"criterion_text":"- Participant has prior severe allergic reaction or intolerance to (zolbetuximab or other monoclonal antibodies, pembrolizumab, mFOLFOX6 or CAPOX)."}
• {"criterion_text":"- Participant has another malignancy for which treatment is required, per investigator’s clinical judgment."}
• {"criterion_text":"- Participant has known dihydropyrimidine dehydrogenase deficiency (screening for dihydropyrimidine dehydrogenase deficiency should be conducted per local requirements). For EU-specific requirements, refer to section 10.9.1 of the protocol."}
• {"criterion_text":"- Participant has known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the participant ineligible)."}
• {"criterion_text":"- Participant has sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if present, should be stable or improving per investigator’s judgment."}
• {"criterion_text":"- Participant has significant cardiovascular disease, including any of the following: a. Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization. b. History of clinically significant ventricular arrhythmias (i.e., sustained; ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes). c. QTc interval > 450 msec for male participants; QTc interval > 470 msec for female participants. d. History or family history of congenital long QT syndrome. e. Cardiac arrhythmias requiring anti-arrhythmic medications (participants with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible)."}
• {"criterion_text":"- Participant has ongoing or previous interstitial lung disease, active diverticulitis or peptic ulcerative disease, or solid organ or stem cell transplant or other uncontrolled or clinically significant medical disorders."}
• {"criterion_text":"- Participant has type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy or skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed"}
• {"criterion_text":"- This criterion has been removed"}
• {"criterion_text":"- Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting."}
• {"criterion_text":"- Participant has significant gastric bleeding and/or untreated gastric ulcers that would preclude the participant from participation per investigator’s judgment."}
• {"criterion_text":"- Participant has unresolved pneumonitis or history of non-infectious pneumonitis such as immune-related pneumonitis, radiation induced pneumonitis."}
• {"criterion_text":"- Participant has history of central nervous system metastases and/or carcinomatous meningitis from gastric/gastroesophageal junction cancer."}
• {"criterion_text":"- Participant has a known history of a positive test for HIV infection or known active hepatitis B (positive HBsAg) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements."}
• {"criterion_text":"- Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization."}
• {"criterion_text":"- Participant has active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization."}
• {"criterion_text":"- Participant has a clinically significant disease or comorbidity that in the opinion of the investigator may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation."}

Primary endpoints

• {"endpoint_text":"- Overall Survival, defined as the time from the date of randomization until the documented date of death from any cause","definition_or_measurement_approach":"Defined as the time from the date of randomization until the documented date of death from any cause"}

Secondary endpoints

• {"endpoint_text":"- Progression-free survival, defined as the time from the date of randomization until the date of radiologic disease progression (investigator-assessed per RECIST V1.1) or death from any cause, whichever is earlier","definition_or_measurement_approach":"Defined as the time from the date of randomization until the date of radiologic disease progression (investigator-assessed per RECIST V1.1) or death from any cause, whichever is earlier"}
• {"endpoint_text":"- Objective response rate, defined as the proportion of participants who have a best overall response of complete response or partial response as investigator-assessed per RECIST V1.1","definition_or_measurement_approach":"Proportion of participants with best overall response of complete response or partial response per investigator assessment using RECIST V1.1"}
• {"endpoint_text":"- Duration of response, defined as the time from the date of the first response (complete response/partial response) until the date of disease progression as investigator-assessed per RECIST V1.1 or date of death from any cause, whichever is earlier","definition_or_measurement_approach":"Time from date of first documented response (CR/PR) to date of radiologic progression (investigator-assessed per RECIST V1.1) or death, whichever occurs first"}
• {"endpoint_text":"- Safety and tolerability of zolbetuximab in combination with pembrolizumab and chemotherapy as evaluated by adverse events, electrocardiogram, vital signs, Eastern Cooperative Oncology Group performance status and safety laboratory assessments (NCI-CTCAE version 5.0)","definition_or_measurement_approach":"Safety and tolerability assessed by adverse events, ECG, vital signs, ECOG performance status and safety labs graded per NCI-CTCAE v5.0"}
• {"endpoint_text":"- Serum concentrations of zolbetuximab: end of infusion concentrations and concentration immediately prior to dosing at multiple dosing","definition_or_measurement_approach":"Pharmacokinetic measurement of serum zolbetuximab concentrations at end of infusion and pre-dose at multiple dosing timepoints"}
• {"endpoint_text":"- Measurement of frequency of antidrug antibody-positive participants","definition_or_measurement_approach":"Assess frequency (incidence) of participants positive for anti-drug antibodies"}

Methods

• Site-based recruitment using patient-facing materials: posters, flyers, brochures and study visit guides (multi-language patient brochures and flyers listed in recruitment documents).
• Direct patient contact via patient letters and thank-you/enrollment cards provided to potential participants.
• Online recruitment postings (K2_OnlinePostings) and digital materials for public-facing recruitment.
• Investigator/referral recruitment through participating oncology clinics and hospitals (site lists provided per country).

Primary sponsor

Full Name

Astellas Pharma Global Development Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Clinical trial services; contact: eu_clinical_trials_information@iqvia.com

Name

Icon Clinical Research Limited

Responsibilities

Multiple sponsor duties listed (codes present); contact: CTISApplications-Pharma@iconplc.com

Name

PPD Development LP

Responsibilities

Sample management / openers (contact: RichmondSMOpeners@ppd.com)

Name

Almac Clinical Services Limited

Responsibilities

Regulatory/compliance support (contact: acsregulatorycompliance@almacgroup.com)

Third parties

• {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Clinical Logistics Inc.","duties_or_roles":"Sample management and logistics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Shin Nippon Biomedical Laboratories Ltd.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"Sample management and logistics","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"Sample Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"Sample Analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}