A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of IMAB362 Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6 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

Phase 1

Conditions: Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
MedDRA 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: EUCTR2017-002567-17-ES

Lead Sponsor: Astellas Pharma Global Development, Inc. (APGD)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 550

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., HIPAA 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., = 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.Female subject must either:
Be of non-childbearing potential:
-postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to Screening, or
-documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy,
bilateral oophorectomy)
Or, if of childbearing potential:
-agree not to try to become pregnant during the study and for 6 months after the final study treatment administration,
and, have a negative serum pregnancy test at Screening, (Note: Subjects with elevated serum beta human chorionic gonadotropin (ßhCG) and a demonstrated non-pregnant status through additional testing are eligible), and if heterosexually active, agree to consistently use 1 form of highly effective birth control* starting at Screening and throughout the study period and for 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 is eligible if:
-Agree to use a male condom starting at screening and continue throughout study treatment and for 6 months after the final study drug administration.
-If he has not had a vasectomy or is not sterile as defined below, his female partner(s) is utilizing 1 form of highly effective birth control starting at Screening and continue throughout study treatment and for 6 months after the he receives his 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 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.
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 HE

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 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 within28 days prior to start of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases >=14 days prior to start of study treatment and has recovered from all acute toxicities is allowed.
3.Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. 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) are allowed.
4.Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
Medical History or Concurrent Disease
5.Subject has prior severe allergic reaction or intolerance to a monoclonal antibody, 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 gastric outlet syndrome or persistent/recurrent vomiting.
10.Subject with recent gastric bleeding or symptomatic subjects with proven gastric ulcers that would exclude the subject from participation per investigator judgment.
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. 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 HCV RNA test results are eligible.
12.Subject has an active autoimmune disease that has required systemic treatment within the past 2 years.
13.Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to start of study treatment.
14.Subject has significant cardiovascular disease, including:
-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 or hypertensive crisis within 6 months prior to administration of first dose of study drug.
-History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
-QTc interval > 450 msec
-Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to first dose of study drugs are eligible)
15.Subject has known active central nervous system metastases and/or carcinomatous meningitis.
16.Subject has known peripheral sensory neuropathy > Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
17.Subject has had a major surgical procedure and has not completel