Brief Summary
Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called GEJ cancer. Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor.
There is an unmet medical need to treat people with advanced stomach cancer or GEJ cancer. This study will give more information about how well zolbetuximab works when given with chemotherapy in adults with advanced stomach cancer or GEJ cancer. In this study, adults with advanced stomach cancer or GEJ cancer will either be given zolbetuximab with chemotherapy or a placebo with chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it. Zolbetuximab with chemotherapy has already been approved to treat stomach cancer and GEJ cancer in some countries. This study is being done in countries where zolbetuximab has not yet been approved for use. If zolbetuximab becomes approved for use in those countries taking part in this study, the people taking part in those countries will leave this study and receive licensed zolbetuximab.
The main aim(s) of the study is(are) to determine the efficacy of zolbetuximab combined with chemotherapy compared to a placebo combined with chemotherapy in treating adults with Claudin 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
Adults with locally advanced unresectable or metastatic stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample of their cancer will also have the Claudin 18.2 protein. They may have been previously treated with certain standard therapies but have not been treated with chemotherapy for their cancer. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.
The study treatments are either zolbetuximab with chemotherapy or placebo with chemotherapy. People who take part will receive just one of the treatments by chance. Study treatment will be double-blinded. That means that the people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in cycles. The study treatment is given to people slowly through a tube into a vein. This is called an infusion. The chemotherapy is called CAPOX (capecitabine and oxaliplatin) and will be given as an infusion and also as tablets. People will have 1 infusion of either zolbetuximab or placebo together with oxaliplatin chemotherapy in 3-week (21-day) cycles. People will also take 1 tablet of capecitabine (chemotherapy) twice a day for the first 2 weeks (14 days) of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the treatment, or they need to start another cancer treatment. People will receive CAPOX for up to about 6 months (8 treatment cycles). After the 6 months, people may receive capecitabine chemotherapy only, until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will visit the clinic on certain days during their treatment. The study doctors will check if people had any medical problems from zolbetuximab or the other study treatments. Also, people in the study will have health checks. On some visits, they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample after their study treatment has finished. People will visit the clinic within 7 days after they stop their study treatment. People will be asked about any medical problems and will have a health check. People who start treatment with licensed zolbetuximab will not need to attend the clinic for further visits and will receive standard of care health checks. People who continue study treatment will visit the clinic at 1 and 3 months after they stop their study treatment. They will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. They will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.
There is an unmet medical need to treat people with advanced stomach cancer or GEJ cancer. This study will give more information about how well zolbetuximab works when given with chemotherapy in adults with advanced stomach cancer or GEJ cancer. In this study, adults with advanced stomach cancer or GEJ cancer will either be given zolbetuximab with chemotherapy or a placebo with chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it. Zolbetuximab with chemotherapy has already been approved to treat stomach cancer and GEJ cancer in some countries. This study is being done in countries where zolbetuximab has not yet been approved for use. If zolbetuximab becomes approved for use in those countries taking part in this study, the people taking part in those countries will leave this study and receive licensed zolbetuximab.
The main aim(s) of the study is(are) to determine the efficacy of zolbetuximab combined with chemotherapy compared to a placebo combined with chemotherapy in treating adults with Claudin 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
Adults with locally advanced unresectable or metastatic stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample of their cancer will also have the Claudin 18.2 protein. They may have been previously treated with certain standard therapies but have not been treated with chemotherapy for their cancer. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.
The study treatments are either zolbetuximab with chemotherapy or placebo with chemotherapy. People who take part will receive just one of the treatments by chance. Study treatment will be double-blinded. That means that the people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in cycles. The study treatment is given to people slowly through a tube into a vein. This is called an infusion. The chemotherapy is called CAPOX (capecitabine and oxaliplatin) and will be given as an infusion and also as tablets. People will have 1 infusion of either zolbetuximab or placebo together with oxaliplatin chemotherapy in 3-week (21-day) cycles. People will also take 1 tablet of capecitabine (chemotherapy) twice a day for the first 2 weeks (14 days) of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the treatment, or they need to start another cancer treatment. People will receive CAPOX for up to about 6 months (8 treatment cycles). After the 6 months, people may receive capecitabine chemotherapy only, until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will visit the clinic on certain days during their treatment. The study doctors will check if people had any medical problems from zolbetuximab or the other study treatments. Also, people in the study will have health checks. On some visits, they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample after their study treatment has finished. People will visit the clinic within 7 days after they stop their study treatment. People will be asked about any medical problems and will have a health check. People who start treatment with licensed zolbetuximab will not need to attend the clinic for further visits and will receive standard of care health checks. People who continue study treatment will visit the clinic at 1 and 3 months after they stop their study treatment. They will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. They will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.
Brief Title
A 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 (GLOW).
Detailed Description
After the marketing approval in Japan on 26 Mar 2024, this study continued as "post marketing clinical study" in Japan. In the rest of the countries which participated in this study, this study continued as clinical study.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer
Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer
Metastatic Gastric Adenocarcinoma or Cancer
Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
* 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 (βhCG) 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) OR
* WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
* Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* A male subject with female partner(s) of childbearing potential:
* must agree to use contraception during the treatment period and for 6 months after the final study treatment administration.
* A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
* 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.
* Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
* Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
* Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects 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.
* Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
* Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
* Subject has ECOG performance status 0 or 1.
* Subject has predicted life expectancy ≥ 12 weeks.
* Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
* Hemoglobin (Hb) ≥ 9 g/dl. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
* Absolute Neutrophil Count (ANC) ≥ 1.5x10\^9/L
* Platelets ≥ 100x10\^9/L
* Albumin ≥ 2.5 g/dL
* Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or \< 3.0 x ULN if liver metastases are present)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
* Estimated creatinine clearance ≥ 30 mL/min
* Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
Exclusion Criteria:
* 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, immunotherapy or other systemic anticancer therapies as long as it was completed at least 6 months prior to randomization.
* Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
* Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to randomization.
* Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. 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 premedication for radiologic imaging contrast use are allowed.
* Subject has received other investigational agents or devices within 28 days prior to randomization.
* Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
* Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
* Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
* Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency.
* Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
* Subject has significant gastric bleeding and/or untreated gastric ulcers that exclude the subject from participation.
* 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 (HBs Ag)) or C infection. NOTE: Screening for these infections should be conducted per local requirements.
* For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
* Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
* Subjects treated for HCV with undetectable viral load results are eligible.
* Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
* Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
* Subject has significant cardiovascular disease, including any of the following:
* Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) or hypertensive crisis within 6 months prior to randomization.
* History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes
* QTc interval \> 450 msec for male subjects; QTc interval \> 470 msec for female subjects
* History or family history of congenital long QT syndrome
* Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for \> 1 month prior to randomization are eligible).
* Subject has a history of central nervous system (CNS) metastases and/or carcinomatous meningitis from gastric/GEJ cancer..
* Subject has known peripheral sensory neuropathy \> grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
* Subject has had a major surgical procedure ≤ 28 days prior to randomization.
* Subject is without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
* Subject has psychiatric illness or social situations that would preclude study compliance.
* Subject has another malignancy for which treatment is required.
* 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.
* 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 (βhCG) 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) OR
* WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
* Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* A male subject with female partner(s) of childbearing potential:
* must agree to use contraception during the treatment period and for 6 months after the final study treatment administration.
* A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
* 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.
* Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
* Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
* Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects 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.
* Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
* Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
* Subject has ECOG performance status 0 or 1.
* Subject has predicted life expectancy ≥ 12 weeks.
* Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
* Hemoglobin (Hb) ≥ 9 g/dl. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
* Absolute Neutrophil Count (ANC) ≥ 1.5x10\^9/L
* Platelets ≥ 100x10\^9/L
* Albumin ≥ 2.5 g/dL
* Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or \< 3.0 x ULN if liver metastases are present)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
* Estimated creatinine clearance ≥ 30 mL/min
* Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
Exclusion Criteria:
* 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, immunotherapy or other systemic anticancer therapies as long as it was completed at least 6 months prior to randomization.
* Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
* Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to randomization.
* Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. 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 premedication for radiologic imaging contrast use are allowed.
* Subject has received other investigational agents or devices within 28 days prior to randomization.
* Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
* Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
* Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
* Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency.
* Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
* Subject has significant gastric bleeding and/or untreated gastric ulcers that exclude the subject from participation.
* 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 (HBs Ag)) or C infection. NOTE: Screening for these infections should be conducted per local requirements.
* For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
* Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
* Subjects treated for HCV with undetectable viral load results are eligible.
* Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
* Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
* Subject has significant cardiovascular disease, including any of the following:
* Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) or hypertensive crisis within 6 months prior to randomization.
* History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes
* QTc interval \> 450 msec for male subjects; QTc interval \> 470 msec for female subjects
* History or family history of congenital long QT syndrome
* Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for \> 1 month prior to randomization are eligible).
* Subject has a history of central nervous system (CNS) metastases and/or carcinomatous meningitis from gastric/GEJ cancer..
* Subject has known peripheral sensory neuropathy \> grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
* Subject has had a major surgical procedure ≤ 28 days prior to randomization.
* Subject is without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
* Subject has psychiatric illness or social situations that would preclude study compliance.
* Subject has another malignancy for which treatment is required.
* 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.
Inclusion Criteria
Inclusion Criteria:
* 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 (βhCG) 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) OR
* WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
* Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* A male subject with female partner(s) of childbearing potential:
* must agree to use contraception during the treatment period and for 6 months after the final study treatment administration.
* A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
* 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.
* Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
* Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
* Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects 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.
* Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
* Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
* Subject has ECOG performance status 0 or 1.
* Subject has predicted life expectancy ≥ 12 weeks.
* Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
* Hemoglobin (Hb) ≥ 9 g/dl. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
* Absolute Neutrophil Count (ANC) ≥ 1.5x10\^9/L
* Platelets ≥ 100x10\^9/L
* Albumin ≥ 2.5 g/dL
* Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or \< 3.0 x ULN if liver metastases are present)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
* Estimated creatinine clearance ≥ 30 mL/min
* Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
* 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 (βhCG) 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) OR
* WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
* Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
* A male subject with female partner(s) of childbearing potential:
* must agree to use contraception during the treatment period and for 6 months after the final study treatment administration.
* A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
* 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.
* Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
* Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
* Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects 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.
* Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
* Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
* Subject has ECOG performance status 0 or 1.
* Subject has predicted life expectancy ≥ 12 weeks.
* Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
* Hemoglobin (Hb) ≥ 9 g/dl. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
* Absolute Neutrophil Count (ANC) ≥ 1.5x10\^9/L
* Platelets ≥ 100x10\^9/L
* Albumin ≥ 2.5 g/dL
* Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or \< 3.0 x ULN if liver metastases are present)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
* Estimated creatinine clearance ≥ 30 mL/min
* Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
Gender
All
Gender Based
false
Keywords
CLDN 18.2
gastroesophageal junction cancer
adenocarcinoma
IMAB362
oxaliplatin
HER2
claudiximab
capecitabine
gastric cancer
HER2 Negative
zolbetuximab
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03653507
Org Class
Industry
Org Full Name
Astellas Pharma Inc
Org Study Id
8951-CL-0302
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
PFS was defined as the time from the date of randomization until the date of radiological progressive disease (PD) (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 by independent review committee \[IRC\]) or death from any cause, whichever was earliest. PD was defined as development of new, or progression of existing metastases to the primary cancer under the study. Kaplan-Meier estimates was used.
Outcome Measure
Progression Free Survival (PFS)
Outcome Time Frame
From the date of randomization until 47 months
Secondary Ids
Secondary Id
2018-000519-26
Secondary Id
CTR20190261
Secondary Id
jRCT2080224166
Secondary Id
2024-511648-16-00
Secondary Outcomes
Outcome Description
OS was defined as the time from the date of randomization until the date of death from any cause. Kaplan-Meier estimates was used.
Outcome Time Frame
From the date of randomization untill 47 months
Outcome Measure
Overall Survival (OS)
Outcome Description
TTCD: time from randomization to first clinically meaning full deterioration (CMFD) that was confirmed at the next scheduled visit.The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status which are scored 1 ("very poor") to 7 ("excellent"). All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. Clinically meaningful deterioration was defined if a participant's change from baseline (CFB) exceeded a pre-specified threshold (as per investigator's discretion) denoting a clinically meaningful change. Kaplan-Meier estimates was used.
Outcome Time Frame
From the date of randomization untill 47 months
Outcome Measure
Time to Confirmed Deterioration (TTCD) Using Physical Functioning as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30)
Outcome Description
TTCD:time from randomization to first CMFD confirmed at next scheduled visit.OG25 evaluated gastric \& gastroesophageal junction cancer-specific symptoms,had 25 items with 6 scales:dysphagia,eating restrictions,reflux,odynophagia,pain, discomfort,anxiety,and 10 single items:trouble with(taste, swallowing saliva, coughing, talking),eating in front of others,dry mouth,body image,choked when swallowing,weight loss and hair loss.STO22: gastric cancer quality of life questionnaire with 22 questions.For OG25 and STO22,items scored on(1:not at all; 2:a little, 3:quite a bit, 4:very much) and 1 question was "yes or no" for STO22.Linear transformation was used; score ranged from 0 to 100;higher score=better level of functioning or greater degree of symptoms. An item from STO22 instrument related to belching was used with OG25. CMFD: if participant's CFB exceeded pre-specified threshold (per investigator's discretion) denoting a clinically meaningful change. Kaplan-Meier (KM) estimates was used.
Outcome Time Frame
From the date of randomization untill 47 months
Outcome Measure
Time to Confirmed Deterioration (TTCD) Using Oesophago-gastric Questionnaire (OG25) on Abdominal Pain and Discomfort as Measured by EORTC QLQ-OG25 Plus STO22 Belching Subscale
Outcome Description
TTCD: time from randomization to first CMFD that was confirmed at the next scheduled visit.The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. Clinically meaningful deterioration was defined if a participant's CFB exceeded a pre-specified threshold (as per investigator's discretion) denoting a clinically meaningful change. Kaplan-Meier estimates was used.
Outcome Time Frame
From the date of randomization untill 47 months
Outcome Measure
Time to Confirmed Deterioration (TTCD) Using Global Health Status as Measured by EORTC QLQ-C30
Outcome Description
ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as was assessed by IRC per RECIST 1.1. CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.
Outcome Time Frame
From the date of randomization untill 47 months
Outcome Measure
Objective Response Rate (ORR)
Outcome Description
DOR was defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings. PD was defined as development of new, or progression of existing metastases to the primary cancer under the study. Kaplan-Meier estimates was used.
Outcome Time Frame
From first response (CR/PR) untill 47 months
Outcome Measure
Duration Of Response (DOR)
Outcome Description
An Adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.TEAE defined as an AE observed after starting administration of the study drug through 30 days after the last dose.
Outcome Time Frame
From first dose untill 47 months
Outcome Measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Outcome Description
ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.
Outcome Time Frame
Baseline, cycle (C) 2 day (D) 1 through C40D1
Outcome Measure
Number of Participant With Eastern Cooperative Oncology Group (ECOG) Performance Status
Outcome Description
The EORTC-QLQ-C30 is a cancer-specific instrument consisting of 5 functional domain scales: physical, role, emotional, social and cognitive.It is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state.
Outcome Time Frame
Baseline, on day (D)1 from cycle (C) 2 through C29, 30-day follow up, 90-day follow up
Outcome Measure
Change From Baseline in Health Related Quality of Life (HRQoL) Measured by the EORTC-QLQ-C30 Questionnaire
Outcome Description
OG25 evaluated gastric \& gastroesophageal junction cancer-specific symptoms,had 25 items with 6 scales:dysphagia,eating restrictions,reflux,odynophagia,pain \& discomfort,anxiety,and 10 single items:trouble with(taste, swallowing saliva, coughing, talking),eating in front of others,dry mouth,body image,choked when swallowing,weight loss and hair loss.STO22: gastric cancer quality of life questionnaire with 22 questions.For OG25 and STO22,items scored on(1:not at all; 2:a little, 3:quite a bit, 4:very much) and 1 question was "yes or no" for STO22.Linear transformation was used; score ranged from 0 to 100;higher score=better level of functioning or greater degree of symptoms. An item from STO22 instrument related to belching was used with OG25.
Outcome Time Frame
Baseline, C2D1 through C29D1, 30-day follow up, 90-day follow up
Outcome Measure
Change From Baseline in HRQoL Measured by the QLQ-OG25 Questionnaire Plus STO22 Belching Subscale Questionnaire
Outcome Description
The GP instrument is a single assessment of overall pain and participants were assessed in global pain according to the following response categories: 1= no pain (anymore), 2 = less pain, 3 = no change and 4 = more pain. Low pain scores are considered a better outcome than a high pain score.
Outcome Time Frame
Baseline, C2D1 through C29D1, 30-day follow up, 90-day follow up
Outcome Measure
Change From Baseline in HRQoL Measured by Global Pain (GP)
Outcome Description
EQ-5D-5L is a standardized instrument for use as a measure of health outcomes consisting of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale for health status.It was developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.
Outcome Time Frame
Baseline, C2D1 through C29D1, 30-day follow up, 90-day follow up
Outcome Measure
Change From Baseline in HRQoL Measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) Questionnaire
Outcome Description
Ctrough was defined as the predose concentration at the end of dosing interval.
Outcome Time Frame
Predose on C2D1,C5D1,C9D1,C13D1,C17D1
Outcome Measure
Pharmacokinetics (PK) of Zolbetuximab in Serum: Trough Concentration (Ctrough)
Outcome Description
Immunogenicity will be measured by the number of participants that are ADA positive.
Outcome Time Frame
Predose on C1D1,C2D1,C5D1,C9D1,C13D1,C17D1, 30-day follow up, 90-day Follow up
Outcome Measure
Number of Anti-drug Antibody (ADA) Positive Participants
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ana Acuna-Villaorduna
Investigator Email
aacunavi@montefiore.org
Investigator Phone