Clinical Trials List
Protocol Number8951-CL-0302
2018-12-25 - 2024-06-30
Phase III
Recruiting4
ICD-9151.0
Malignant neoplasm of cardia of stomach
A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus CAPOX Compared with Placebo Plus CAPOX as First-line Treatment of Subjects with Claudin (CLDN) 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
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Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
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Sponsor
Astellas Pharma Global Development, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 鄭紹彬 Division of General Internal Medicine
- SHAO-CIAO LUO Division of General Internal Medicine
- CHENG-HSIEN LIN Division of General Internal Medicine
- Tsung -Chih Chen Division of General Internal Medicine
- 林欣 Division of General Internal Medicine
- YU-HSUAN SHIH Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chih-Ming Chou Division of General Internal Medicine
- Chang-Yun Lu Division of General Internal Medicine
- Wei-Wen Chang Division of General Internal Medicine
- 謝茂 Division of General Internal Medicine
- 方嘉郎 Division of General Internal Medicine
- Mao-Chih Hsieh Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- 林建良 Division of General Internal Medicine
- 陳昭勳 Division of General Internal Medicine
- 曹朝榮 Division of General Internal Medicine
- 陳彥勳 Division of General Internal Medicine
- 蕭聖諺 Division of General Internal Medicine
- 黃文聰 Division of General Internal Medicine
- Shang-Wen Chen Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- Ta-Chih Liu Division of General Internal Medicine
- Hui-Ching Wang Division of General Internal Medicine
- Fang-Jung Yu Yu Division of General Internal Medicine
- Li-Tzong Chen Division of General Internal Medicine
- 蔡郁棻 Division of General Internal Medicine
- Yi-Chang Liu Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Patients with Claudin (CLDN) 18.2 positive, HER2 negative, locally advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma
Objectives
Primary
To evaluate the efficacy of zolbetuximab plus capecitabine and oxaliplatin (CAPOX) compared
with placebo plus CAPOX (as first-line treatment) as measured by Progression Free Survival
(PFS) in subjects with Claudin (CLDN) 18.2-positive, human epidermal growth factor receptor 2
(HER2)-negative locally advanced unresectable or metastatic gastric and gastroesophageal
junction (GEJ) adenocarcinoma
Secondary
To evaluate efficacy as measured by Overall Survival (OS) as a key secondary objective
To evaluate efficacy as measured by Objective Response Rate (ORR)
To evaluate efficacy as measured by Duration of Response (DOR)
To evaluate safety and tolerability of zolbetuximab
To evaluate health related quality of life (HRQoL) using the parameters as measured by European
Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire
(QLQ)-C30 and QLQ-OG25 plus STO22 Belching subscale, Global Pain (GP) and the EuroQOL
Five Dimensions Questionnaire 5L (EQ5D-5L) questionnaires
To evaluate the pharmacokinetics of zolbetuximab
To evaluate the immunogenicity profile of zolbetuximab
Exploratory
To evaluate efficacy as measured by Time to Progression (TTP)
To evaluate PFS following subsequent anticancer treatment (PFS2)
To evaluate Disease Control Rate (DCR)
To evaluate potential genomic and/or other biomarkers that may correlate with treatment outcome
to zolbetuximab and CAPOX.
To evaluate Health Resource Utilization (HRU)
Test Drug
Zolbetuximab (IMAB362)
Active Ingredient
Zolbetuximab (IMAB362)
Dosage Form
vial
Dosage
105
Endpoints
Primary:
1.PFS, defined as the time from the date of randomization until the date of radiological PD (per RECIST 1.1 by IRC) or death from any cause, whichever is earliest
Secondary:
1.OS, defined as the time from the date of randomization until the date of death from any cause
2.ORR, defined as the proportion of subjects who have a best overall response of complete response(CR) or partial response(PR) as assessed by IRC per RECIST 1.1
3.DOR, defined as the time from the date ofthe first response (CRlPR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death form any cause, whichever is earliest
4.Safety and tolerability, as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status
5.HRQoL, as collected via EORTC QLQ-C30, QLQ-OG25 plus ST022 Belching subscale, GP, and EQ5D-5L questionnaires
6.Pharmacokinetics of zolbetuximab, Ctrough
7.Immunogenicity of zolbetuximab as measured by the frequency of antidrug-antibody (ADA) positive subjects
Exploratory:
1.The time to disease progression (TTP) ,as the time from the day of random assignment to the assessment of progression (PD) according to the solid tumor response assessment criteria (per RECIST 1.1 by IRC)
2.PFS2, as the time between the date of random assignment and subsequent anti-cancer treatment after disease progression (assessed by the trial host), death from any cause, or the start of any other anti-cancer treatment (whichever occurs first)
3.DCR , as the proportion of subjects who obtained the best overall response of CR, PR or SD according to per RECIST 1.1 by IRC
4.Potential genomics and/or other exploratory biomarkers that may be related to the outcome of zolbetuximab treatment
5.HRU, as healthy resource utilization
1.PFS, defined as the time from the date of randomization until the date of radiological PD (per RECIST 1.1 by IRC) or death from any cause, whichever is earliest
Secondary:
1.OS, defined as the time from the date of randomization until the date of death from any cause
2.ORR, defined as the proportion of subjects who have a best overall response of complete response(CR) or partial response(PR) as assessed by IRC per RECIST 1.1
3.DOR, defined as the time from the date ofthe first response (CRlPR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death form any cause, whichever is earliest
4.Safety and tolerability, as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status
5.HRQoL, as collected via EORTC QLQ-C30, QLQ-OG25 plus ST022 Belching subscale, GP, and EQ5D-5L questionnaires
6.Pharmacokinetics of zolbetuximab, Ctrough
7.Immunogenicity of zolbetuximab as measured by the frequency of antidrug-antibody (ADA) positive subjects
Exploratory:
1.The time to disease progression (TTP) ,as the time from the day of random assignment to the assessment of progression (PD) according to the solid tumor response assessment criteria (per RECIST 1.1 by IRC)
2.PFS2, as the time between the date of random assignment and subsequent anti-cancer treatment after disease progression (assessed by the trial host), death from any cause, or the start of any other anti-cancer treatment (whichever occurs first)
3.DCR , as the proportion of subjects who obtained the best overall response of CR, PR or SD according to per RECIST 1.1 by IRC
4.Potential genomics and/or other exploratory biomarkers that may be related to the outcome of zolbetuximab treatment
5.HRU, as healthy resource utilization
Inclution Criteria
General Criteria:
1. lnstitutional Review Board (IRB)/lndependent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health lnsurance Portability and Accountability Act [HIP AA] Authorization for US sites) must be obtained from the subject or legally authorized representative (if applicable) prior to any study-related procedures.
2. Subject is considered an adult (e.g.，≥618 years of age in the US) according to local regulation at the time of signing the informed consent.
3. A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin (ßhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3 Contraception Requirements]
OR
WOCBP who agrees to follow the contraceptive guidance as defined in [Appendix 12.3 Contraception Requirements] throughout the treatment period and for 6 months after the final study treatment administration
4. Female subject must agree not to breastfeed starting screening and throughout the study period, and for 6 months after the final study treatment administration.
5. Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
6. A male subject with female partner(s) of childbearing potential: must agree to use contraception as detailed in [Appendix 12.3 Contraception Requirements] during the treatment period and for 6 months after the final study treatment administration.
7. A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
8. 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 treatment administration.
9. Subject agrees not to participate in another interventional study while receiving study drug in present study.
10. Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
11. Subject has radiologically confmned locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
12. Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
l3. Subject's tumor expresses CLDN18.2 in≥75%oftumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
14. Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
Physical or Laboratory Findings:
15. Subject has ECOG performance status 0 or 1.
16. Subject has predicted life expectancy ≥ 12weeks in the opinion of the investigator.
17. Subject must meet all of the following criteria based on the centrally analyzed laboratory tests 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 to determine eligibility.
●Hemoglobin (Hb)≥9g/dl. NOTE: subject must not have received any growth factor or blood transfusions within 14 days prior to the hematology values obtained at screening. Subjects requiring transfusions to meet eligibility criteria缸enot eligible.
●Absolute Neutrophil Count (ANC)≥1.5x l09/L
●Platelets≥100xl09/L
●Albumin≥2.5g/dL
●Total Bilirubin≤1.5x upper limit of normal (ULN)
●Aspartate aminotransferase (AST) and alanine aminotransferase (AL T)≤2.5xULN without liver metastases (or≤ 5 x ULN if liver metastases are present)
●Estimated creatinine clearance≥30mL/min
●Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT)≤1.5x ULN (except for subjects receiving anticoagulation therapy)
1. lnstitutional Review Board (IRB)/lndependent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health lnsurance Portability and Accountability Act [HIP AA] Authorization for US sites) must be obtained from the subject or legally authorized representative (if applicable) prior to any study-related procedures.
2. Subject is considered an adult (e.g.，≥618 years of age in the US) according to local regulation at the time of signing the informed consent.
3. A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin (ßhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3 Contraception Requirements]
OR
WOCBP who agrees to follow the contraceptive guidance as defined in [Appendix 12.3 Contraception Requirements] throughout the treatment period and for 6 months after the final study treatment administration
4. Female subject must agree not to breastfeed starting screening and throughout the study period, and for 6 months after the final study treatment administration.
5. Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
6. A male subject with female partner(s) of childbearing potential: must agree to use contraception as detailed in [Appendix 12.3 Contraception Requirements] during the treatment period and for 6 months after the final study treatment administration.
7. A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
8. 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 treatment administration.
9. Subject agrees not to participate in another interventional study while receiving study drug in present study.
10. Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
11. Subject has radiologically confmned locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
12. Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
l3. Subject's tumor expresses CLDN18.2 in≥75%oftumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
14. Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
Physical or Laboratory Findings:
15. Subject has ECOG performance status 0 or 1.
16. Subject has predicted life expectancy ≥ 12weeks in the opinion of the investigator.
17. Subject must meet all of the following criteria based on the centrally analyzed laboratory tests 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 to determine eligibility.
●Hemoglobin (Hb)≥9g/dl. NOTE: subject must not have received any growth factor or blood transfusions within 14 days prior to the hematology values obtained at screening. Subjects requiring transfusions to meet eligibility criteria缸enot eligible.
●Absolute Neutrophil Count (ANC)≥1.5x l09/L
●Platelets≥100xl09/L
●Albumin≥2.5g/dL
●Total Bilirubin≤1.5x upper limit of normal (ULN)
●Aspartate aminotransferase (AST) and alanine aminotransferase (AL T)≤2.5xULN without liver metastases (or≤ 5 x ULN if liver metastases are present)
●Estimated creatinine clearance≥30mL/min
●Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT)≤1.5x ULN (except for subjects receiving anticoagulation therapy)
Exclusion Criteria
Main exclusion criteria:
Waivers to the exclusion criteria will NOT be allowed.
Subject who meets any ofthe following exclusion criteria prior to enrollment is not eligible for enrollment: Prohibited Treatment or Therapies:
1. Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
2. Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma unless the radiotherapy was completed > 28 days prior to the first dose of study treatment. Subject who received palliative radiotherapy to perpheral bone metastases≥14days prior to first dose of study treatment and has recovered from all acute toxicities is eligible.
3. Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to first dose of study treatment.
4. Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject 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) or a single dose of systemic corticosteroids is eligible.
5. Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
Medical History or Concurrent Disease:
6. Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
7. Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
8. Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
9. Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements.)
10. Subject has gastric outlet syndrome or persistent/recurrent vomiting.
11. Subject had recent gastric bleeding and/or is symptomatic with proven gastric ulcers that excludes the subject from participation per investigator judgement.
12. Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive HBs Ag) or C infection. 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 serology but negative hepatitis C virus (HCV) RNA test results are eligible.
13. Subject has an active autoimmune disease that has required systemic treatment within the past 2 years. 14. Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to first dose of study treatment.
15. Subject has significant cardiovascular disease, including any of the following:
a) Congestive heart failure (defined as New York Heart Association [NYHA] Class III 01' IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to administration of first dose of study treatment;
b) History of clinically significant ventricular arrhythrnias (i.e., sustained ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes);
c) QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects;
d) History or family history of congenital long QT syndrome
e) Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible.)
16. Subject has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
17. Subject has known peripheral sensory neuropathy > grade 1 unless the absence of deep tendon ref1exes is the sole neurological abnormality.
18. Subject has had a major surgical procedure 28 days prior to the first dose of study treatment. (a) Subject is without complete recovery from a major surgical procedure≤14days prior to the first dose of study treatment.
19. Subject has psychiatric illness or social situations that would preclude study compliance, per investigator judgement.
20. Subject has another malignancy for which treatment is required per investigator's clinical judgment
21. Subject has any concurrent disease, infection, or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.
Waivers to the exclusion criteria will NOT be allowed.
Subject who meets any ofthe following exclusion criteria prior to enrollment is not eligible for enrollment: Prohibited Treatment or Therapies:
1. Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
2. Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma unless the radiotherapy was completed > 28 days prior to the first dose of study treatment. Subject who received palliative radiotherapy to perpheral bone metastases≥14days prior to first dose of study treatment and has recovered from all acute toxicities is eligible.
3. Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to first dose of study treatment.
4. Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject 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) or a single dose of systemic corticosteroids is eligible.
5. Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
Medical History or Concurrent Disease:
6. Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
7. Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
8. Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
9. Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements.)
10. Subject has gastric outlet syndrome or persistent/recurrent vomiting.
11. Subject had recent gastric bleeding and/or is symptomatic with proven gastric ulcers that excludes the subject from participation per investigator judgement.
12. Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive HBs Ag) or C infection. 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 serology but negative hepatitis C virus (HCV) RNA test results are eligible.
13. Subject has an active autoimmune disease that has required systemic treatment within the past 2 years. 14. Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to first dose of study treatment.
15. Subject has significant cardiovascular disease, including any of the following:
a) Congestive heart failure (defined as New York Heart Association [NYHA] Class III 01' IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to administration of first dose of study treatment;
b) History of clinically significant ventricular arrhythrnias (i.e., sustained ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes);
c) QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects;
d) History or family history of congenital long QT syndrome
e) Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible.)
16. Subject has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
17. Subject has known peripheral sensory neuropathy > grade 1 unless the absence of deep tendon ref1exes is the sole neurological abnormality.
18. Subject has had a major surgical procedure 28 days prior to the first dose of study treatment. (a) Subject is without complete recovery from a major surgical procedure≤14days prior to the first dose of study treatment.
19. Subject has psychiatric illness or social situations that would preclude study compliance, per investigator judgement.
20. Subject has another malignancy for which treatment is required per investigator's clinical judgment
21. Subject has any concurrent disease, infection, or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.
The Estimated Number of Participants
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Taiwan
41 participants
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Global
2333 participants
