ZOLBETUXIMAB for Advanced gastric adenocarcinoma | Gastroesophageal junction adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable)."}
• {"criterion_text":"- Cohorts 1-4: Subject has radiographically-confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to the first dose of study treatment."}
• {"criterion_text":"- Subject's tumor sample has CLDN18.2 expression, demonstrating moderate to strong membranous staining as determined by central IHC testing."}
• {"criterion_text":"- Subject agrees not to participate in another interventional study while on treatment."}
• {"criterion_text":"- Subject has ECOG performance status 0 to 1."}
• {"criterion_text":"- Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator."}
• {"criterion_text":"- Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to the first dose of study treatment. In case of multiple central laboratory data within this period, the most recent data should be used. - Hemoglobin (Hgb) ≥ 9 g/dL (transfusion is allowed, but posttransfusion Hgb [24 hours or later following transfusion] must be ≥ 9 g/dL) - Absolute neutrophil count (ANC) ≥ 1.5 × 109/L - Platelets ≥ 100 × 109/L - Albumin ≥ 2.5 g/dL - Total bilirubin ≤ 1.5 × upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN in subjects without liver metastases (≤ 5 × ULN if liver metastases are present) - Cohorts 1-4: Estimated creatinine clearance ≥ 30 mL/min - Cohort 5: Serum creatinine <1.5 × ULN, or estimated creatinine clearance > 50 mL/min for subjects with serum creatinine levels > 1.5 × ULN - Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × ULN (except for subjects receiving anticoagulation therapy)"}
• {"criterion_text":"- Subject is considered an adult according to local regulation at the time of signing informed consent."}
• {"criterion_text":"- Female subject is eligible to participate if she is not pregnant [See Appendix 12.6 Contraception Requirements] and at least one of the following conditions applies: a. Not a woman of child-bearing potential (WOCBP) as defined in Appendix 12.6 Contraception Requirements OR b. WOCBP who agrees to follow the contraceptive guidance as defined in Appendix 12.6 Contraception Requirements throughout the treatment period and for at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs"}
• {"criterion_text":"- Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration."}
• {"criterion_text":"- Female subject must agree not to donate ova starting at screening and throughout the study, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs."}
• {"criterion_text":"- A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception as detailed in Appendix 12.6 Contraception Requirements during the treatment period and for at least 6 months after the final study drug administration."}
• {"criterion_text":"- Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration."}
• {"criterion_text":"- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration."}
• {"criterion_text":"- Subject has histologically confirmed gastric or GEJ adenocarcinoma."}

Exclusion criteria

• {"criterion_text":"- Subject has had prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies"}
• {"criterion_text":"- Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to the start of study treatment."}
• {"criterion_text":"- Subject has active autoimmune disease that has required systemic treatment within the past 3 months prior to the start of study treatment."}
• {"criterion_text":"- Subject has a clinically significant disease or co-morbidity that in the opinion of the investigator may adversely affect the safe delivery of treatment within this study or make the subject unsuitable for study participation."}
• {"criterion_text":"- Subject has psychiatric illness or social situations that would preclude study compliance per investigator's judgment."}
• {"criterion_text":"- Subject has had a major surgical procedure less or equal to 28 days before start of study treatment."}
• {"criterion_text":"- Subject is without complete recovery from a major surgical procedure less or equal to 14 days before start of study treatment."}
• {"criterion_text":"- Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma less or equal to 14 days (Cohorts 1 and 3A) and less or equal to 28 days (Cohorts 2 and 4A or 4B) prior to start of study treatment and has NOT recovered from any related toxicity."}
• {"criterion_text":"- Subject has another malignancy for which treatment is required, per investigator's clinical judgment."}
• {"criterion_text":"- Subject has known immediate or delayed hypersensitivity or contraindication to any component of study treatment."}
• {"criterion_text":"- Subject has received other investigational agents or devices concurrently or within 28 days prior to first dose of study treatment."}
• {"criterion_text":"- Subject has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study treatment. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast use are allowed."}
• {"criterion_text":"- Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting."}
• {"criterion_text":"- Per investigator judgment, subject has significant gastric bleeding and/or untreated gastric ulcers that would preclude the subject from participation per investigator judgment."}
• {"criterion_text":"- Subject has history of active central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer."}
• {"criterion_text":"- Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen [HBsAg]) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements. - For subjects who are negative for HBs Ag, but HBc Ab positive, an HB DNA test will be performed and if positive the subject will be excluded. - Subjects with positive hepatitis C virus (HCV) serology, but negative HCV RNA test results are eligible. - Subjects treated for HCV with undetectable viral load results are eligible."}
• {"criterion_text":"- Subject has had within 6 months prior to first dose of study treatment any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure."}

Primary endpoints

• {"endpoint_text":"- ORR of Zolbetuximab as a single agent by independent review central reader","definition_or_measurement_approach":"Objective response rate (ORR) of zolbetuximab as a single agent as assessed by an independent central reader."}

Secondary endpoints

• {"endpoint_text":"- Pharmacokinetics of zolbetuximab (Cohorts 1A, 2, 3A, 4 and 5): AUCinf, AUCinf[%extrap], AUClast, AUCtau, Cmax, Ctrough, tmax, t1/2, tlast,CL, Vz, as appropriate","definition_or_measurement_approach":"PK parameters for zolbetuximab (AUCinf, AUClast, AUCtau, Cmax, Ctrough, tmax, t1/2, tlast, CL, Vz) measured in specified cohorts."}
• {"endpoint_text":"- Pharmacokinetics of oxaliplatin (Cohort 2) and 5-FU (Cohort 2): AUCinf, AUCinf[%extrap], AUClast, Cmax, tmax, t1/2, tlast,CL, Vz, as appropriate","definition_or_measurement_approach":"PK parameters for oxaliplatin and 5-FU in Cohort 2 (AUCinf, AUClast, Cmax, tmax, t1/2, tlast, CL, Vz)."}
• {"endpoint_text":"- Safety and tolerability of single agent zolbetuximab, in combination with mFOLFOX6 (with or without nivolumab), in combination with pembrolizumab, and in combination with FLOT evaluated by AEs, ECG, vital signs, ECOG performance status and laboratory assessments (NCICTCAE version 4.03)","definition_or_measurement_approach":"Safety assessed by adverse events, ECG, vital signs, ECOG PS and laboratory assessments per NCI-CTCAE v4.03."}
• {"endpoint_text":"- Safety and tolerability of zolbetuximab + FLOT in Cohort 5 include the following additional assessments: surgical complications, surgical mortality as defined by death within 30 days of surgery, percentage of subjects able to complete preoperative chemotherapy, perioperative mortality and morbidity at 30 days and 90 days post last dose, percentage of subjects able to start postoperative chemotherapy, percentage of subjects able to complete postoperative chemotherapy","definition_or_measurement_approach":"Cohort 5-specific safety endpoints including surgical complications, surgical mortality (death within 30 days), perioperative mortality/morbidity at 30 and 90 days, and chemotherapy completion rates."}
• {"endpoint_text":"- Immunogenicity of zolbetuximab as a single agent, in combination with mFOLFOX6 (with or without nivolumab), in combination with pembrolizumab and in combination with FLOT as measured by the frequency of anti-drug antibody (ADA) positive subjects","definition_or_measurement_approach":"Immunogenicity measured by frequency of ADA-positive subjects."}
• {"endpoint_text":"- HHRQoL measured by the QLQ-C30, OG-25, GP, EuroQOL Five Dimensions Questionnaire (EQ-5D) and the HRU questionnaires","definition_or_measurement_approach":"Health-related quality of life assessed using QLQ-C30, OG-25, GP, EQ-5D and HRU questionnaires."}
• {"endpoint_text":"- ORR of zolbetuximab in combination with pembrolizumab and in combination with mFOLFOX6 as assessed by an independent central reader","definition_or_measurement_approach":"ORR for combination regimens assessed by an independent central reader."}
• {"endpoint_text":"- ORR of zolbetuximab as a single agent, in combination with mFOLFOX6 (with or without nivolumab) and in combination with pembrolizumab by investigator assessment","definition_or_measurement_approach":"ORR by investigator assessment for single-agent and combination regimens."}
• {"endpoint_text":"- DCR, DOR and PFS of zolbetuximab as a single agent, in combination with mFOLFOX6 (with or without nivolumab) and in combination with pembrolizumab as assessed by an independent central reader","definition_or_measurement_approach":"Disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS) assessed by independent central reader."}
• {"endpoint_text":"- DCR, DOR and PFS of zolbetuximab as a single agent, in combination with mFOLFOX6 (with or without nivolumab) and in combination with pembrolizumab as assessed by the investigator","definition_or_measurement_approach":"DCR, DOR and PFS assessed by investigator."}
• {"endpoint_text":"- OS of zolbetuximab as a single agent, in combination with mFOLFOX6 and nivolumab, and in combination with FLOT","definition_or_measurement_approach":"Overall survival (OS) for single agent and combination regimens."}
• {"endpoint_text":"- Cohort 5 only: Antitumor activity of zolbetuximab and FLOT as measured by radiological response (restaging) and pathological response ypTNM (pCR)","definition_or_measurement_approach":"Cohort 5 antitumor activity measured by radiological restaging and pathological ypTNM (pCR)."}
• {"endpoint_text":"- Cohort 5 only: DFS","definition_or_measurement_approach":"Disease-free survival (Cohort 5 only)."}
• {"endpoint_text":"- Cohort 5 only: Minimal residual disease and disease recurrence as measured by circulating tumor DNA (ctDNA)","definition_or_measurement_approach":"Minimal residual disease and recurrence measured by ctDNA."}

Italy

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

681

Number Of Sites

4

Number Of Participants

24

France

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

683

Number Of Sites

4

Number Of Participants

24

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

IVRS treatment randomisation; contact: eu_clinical_trials_information@iqvia.com

Name

Parexel International (IRL) Limited

Responsibilities

Clinical trial services (sponsorDuties code 5); contact: Clinicaltrial.Enquiries@parexel.com

Name

Fortrea Inc.

Responsibilities

Statistical programming and related services (codes 15,6,10); contact: submissions@fortrea.com

Name

Almac Clinical Services Limited

Responsibilities

Clinical supply chain support, IP management (code 15); contact: dcsupport@almacgroup.com

Name

CMIC Inc.

Responsibilities

Clinical vendor activities (sponsorDuties code 7); contact: CMICINC-BIOA@cmicgroup.com

Third parties

• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Clinical Supply Chain Support IP management (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cmic Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Shin Nippon Biomedical Laboratories Ltd.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: 4, 5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"Clinical Supply Chain Support IP management (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties codes: 10, 15 (Statistical programming), 6","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"IVRS treatment randomisation (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"BioAgilytix Europe GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"biorepository (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"provision of CLND 18.2 assay test kits (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: 5","organisation_type":"Pharmaceutical company"}