A Phase 3 efficacy, safety and tolerability study of zolbetuximab (experimental drug) plus mFOLFOX6 chemotherapy compared to placebo plus mFOLFOX6 as treatment for gastric and gastroesophageal junction (GEJ) cancer
- Conditions
- Gastric adenocarcinoma and Gastroesophageal Junction (GEJ) adenocarcinoma
- Registration Number
- JPRN-jRCT2080224032
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 566
1. Female subject eligible to participate if she is not pregnant and at least one of the following conditions applies:
a. Not a woman of child-bearing potential (WOCBP) OR
b. WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs
2. 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.
3. 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.
4. A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
5. 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.
6. 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.
7. Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
8. Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
9. 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.
10. Subject's tumor expresses CLDN18.2 in => 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
11. Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
12. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
13. Subject has predicted life expectancy => 12 weeks.
14. 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.
a. Hemoglobin (Hgb) => 9 g/dL. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb => 9 g/dL.
b. Absolute neutrophil count (ANC) => 1.5 x 10^9/L.
c. Platelets => 100 x 10^9/L.
d. Albumin => 2.5 g/dL.
e. Total bilirubin =< 1.5 x upper limit of normal (ULN) without liver metastases (or < 3.0 x ULN if liver metastases are present)
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN without liver metastases (or =< 5 x ULN if liver metastases are present)
g. Estimated creatinine clearance => 30 mL/min
h. Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin
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, immunotherapy 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 systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization.
4. Subject has received other investigational agents or devices within 28 days prior to randomization.
5. Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
6. Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
7. Subject has prior severe allergic reaction or intolerance to any component of mFOLFOX6.
8. Subject has known dihydropyrimidine dehydrogenase deficiency.
9. Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
10. Subject has significant gastric bleeding and/or untreated gastric ulcers that would exclude the subject from participation.
11. 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.
12. Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
13. Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
14. Subject has significant cardiovascular disease, including any of the following:
a. Congestive heart failure (defined as New York Heart Association [NHYA] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization.
b. History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes)
c. QTc interval > 450 msec for male 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 (Subject with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
15. Subject has a history of central nervous system (CNS) metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
16. Subject has known peripheral sensory neuropathy > Grade 1.
17. 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.
18. Subject has psychiatric illness or social situations that would preclude study compliance.
19. Subject has another malignancy for which treatment is required.
20. Subject has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which place
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - Progression-free survival (PFS)
- Secondary Outcome Measures
Name Time Method - Overall survival (OS) <br>- Objective Response Rate (ORR)<br>- Duration Of Response (DOR)<br>- Adverse events (AEs)<br>- Laboratory assessments, vital signs, electrocardiograms (ECG) <br>- Eastern Cooperative Oncology Group (ECOG) performance status <br>- Health Related Quality of Life (HRQoL)<br> - measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire 30 (EORTC QLQ-C30), QLQ- Oesophago-Gastric Module 25 (OG25), Global Pain (GP), and EuroQOL Five Dimensions Questionnaire 5L (EQ5D-5L). <br>- Time to confirmed deterioration (TTCD)<br> - calculated based on physical functioning measured by EORTC QLQ-C30 and QLQ-25, OG25-Pain, and general health status/quality of life (GHS/QoL). <br>- Pharmacokinetics of zolbetuximab, Ctrough <br>- Immunogenicity of zolbetuximab as mensurated by the frequency of anti-drug antibody (ADA).