Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma MedDRA version: 20.0 Level: PT Classification code 10001150 Term: Adenocarcinoma gastric System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Zolbetuximab (IMAB362)
Product Code: Zolbetuximab (IMAB362)
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or P
Sponsors
Astellas Pharma Global Development, Inc. (APGD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Criteria: 1.Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] Authorization for US sites) must be obtained from the subject or legally authorized representative (if applicable) prior to any studyrelated 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.Subject agrees not to participate in another interventional study while on study treatment. 4.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: a.Not a woman of childbearing potential (WOCBP) as defined in Appendix 12.3 Contraception Requirements OR b.WOCBP who agrees to follow the contraceptive guidance as defined in Appendix 12.3 Contraception Requirements throughout the treatment period and for at least 6 months after the final study drug administration. 5.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. 6.Female subject must not donate ova starting at Screening and throughout the study period, and for 6 months after the final study drug administration. 7.A sexually active male subject with female partner(s) who are of childbearing potential must agree to use contraception as detailed in Appendix 12.3 Contraception Requirements during the treatment period and for at least 6 months after the final study drug administration. 8.Male subject must not donate sperm starting at Screening and throughout the study period and for 6 months after the final study drug administration. 9.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 for the time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration. 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 nonmeasurable disease according to RECIST 1.1), per local assessment, = 28 days prior to randomization. For subjects with only 1 evaluable
Exclusion criteria
Exclusion criteria: 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 randomization. Subject may have received treatment with herbal medications that have known antitumor activity > 28 days prior randomization. 2.Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma = 14 days prior to randomization and recovered from any related toxicity. 3.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. 4.Subject has received other investigational agents or devices within 28 days prior to randomization. Medical History or Concurrent Disease 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 (DPD). (NOTE: Screening for DPD deficiency should be conducted per local requirements.) 9.Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting. 10.Per investigator judgment, subject has significant gastric bleeding and/or untreated gastric ulcers that 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 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 (HCV) serology, but negative HCV RNA test are eligible. c.Subjects treated with HCV with undetectable viral load results are eligible. 12.Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of zolbetuximab plus mFOLFOX6 compared with placebo plus mFOLFOX6 (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 Objective: - 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) QLQ-C30, QLQ-OG25, 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 - To evaluate efficacy as measured by Time to Progression (TTP) - To evaluate PFS following subsequent anti-cancer 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 mFOLFOX6. - To evaluate Health Resource Utilization(HRU) ; Primary end point(s): The primary endpoint is PFS, which is defined as the time from the date of randomization until the date of radiological PD (per Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 by independent review committee [IRC]) or death from any cause, whichev | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: -OS, defined as the time from the date of randomization until the date of death from any cause -ORR, defined as the proportion of subjects who have a best overall response (BOR) of CR or PR as assessed by IRC per RECIST 1.1 -DOR, 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 -Safety and tolerability, as measured by AEs, laboratory test results, vital signs, electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) performance status -HRQoL, as collected via EORTC QLQ-C30, QLQ-OG25, GP and EQ5D-5L questionnaires -Pharmacokinetics of IMAB362, Cmax and Ctrough -Immunogenicity of IMAB362 as measured by the frequency of anti-drug antibody (ADA) positive subjects. The exploratory endpoints are: -TTP, defined as the time from the date of randomization until the date of PD as assessed by IRC per RECIST 1.1. -PFS2, defined as the time from the date of randomization until the date of PD (per investigator) following subsequent anti-cancer therapy, death from any cause or start of any other anti-cancer therapy, whichever is earliest. -DCR, defined as the proportion of subjects who have a BOR of SD, CR or PR as assessed by IRC per RECIST 1.1. -Potential genomic and/or other exploratory biomarkers that may be related to treatment outcome of IMAB362 -HRU ;Timepoint(s) of evaluation of this end point: The secondary endpoint analysis will be performed at the protocol defined primary PFS analysis and at the final OS analysis after 100% of the planned death events have been observed. | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Costa Rica, France, Germany, Israel, Italy, Japan, Korea, Republic of, Mexico, Peru, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactService Desk - Global Clinical Dev.
Astellas Pharma Europe B.V.
Outcome results
None listed