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
- Conditions
- Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric orGastroesophageal Junction (GEJ) AdenocarcinomaMedDRA version: 20.0Level: PTClassification code 10001150Term: Adenocarcinoma gastricSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000519-26-IE
- Lead Sponsor
- Astellas Pharma Global Development, Inc. (APGD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
General Criteria:
1. 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 (if applicable) prior to any study-related procedures.
2. Subject is considered an adult (e.g., = 18 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 9 months after the final administration of oxaliplatin 6 months after the final administration of all other study drugs.
4. 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.
5. 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.
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.
Disease Specific Criteria:
10. Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
11. Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
12. Subject has radiologically evaluable disease (measurable and/or non-measurable) 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.
13. Subject’s tumor expresses CLDN18.2 in = 75% of tumor 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 = 12 weeks in the opinion of the investigator.
17. Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests colle
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 , immunotherpay or other systemic anticancer therapies as long as it was completed at least 6 months prior to randomization.
2. 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.
3. Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to randomization.
4. Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. 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), receiving a single dose of systemic corticosteroids,
or receiving systemic corticosteroids as premedication for radiologic imaging contrast use is eligible.
5. Subject has received other investigational agents or devices within 28 days prior to randomization.
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 a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
11. Per investigator judgement, subject has significant gastric bleeding and/or untreated gastric ulcers that exclude the subject from participation.
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. NOTE: Screening for these infections should be conducted per local requirements.
a. 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.
b. Subjects with positive hepatitis C virus (HCV) serology but negative HCV RNA test are eligible.
c. Subjects treated for HCV with undetectable viral load results are eligible.
13. Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
14. Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
15. Subject has significant cardiovascular disease, including any of the following:
a. Congestive heart failure (defined as New York Heart Association [NYHA] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), 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 Poi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method