Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

The purpose of this study is to evaluate the efficacy of zolbetuximab plus mFOLFOX6 compared with placebo plus mFOLFOX6 (as first-line treatment) as measured by Progression Free Survival (PFS). This study will also evaluate efficacy, safety and tolerability of zolbetuximab, as well as its effects on quality of life. Pharmacokinetics (PK) of zolbetuximab and the immunogenicity profile of zolbetuximab will be evaluated as well.

Official Title

A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (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

Details

The study consists of the following periods: screening; treatment; post-treatment follow up, safety follow up, long term and survival follow-up.

Keywords

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 HER2 IMAB362 leucovorin fluorouracil Gastric cancer claudiximab zolbetuximab oxaliplatin adenocarcinoma Gastro-Esophageal Junction cancer HER2 Negative mFOLFOX6 Antibodies, Monoclonal

Eligibility

You can join if…

Open to people ages 18 years and up

  • Female subject eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin and a demonstrated non-pregnant status through additional testing are eligible) and at least one of the following conditions applies:
  • Not a woman of child-bearing potential (WOCBP) OR
  • WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration
  • 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.
  • Female subject must agree not to donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
  • 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.
  • 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.
  • 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.
  • 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 the first dose of study treatment.
  • 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.
  • Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC)testing.
  • Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
  • Subject has ECOG performance status 0 to 1.
  • Subject has predicted life expectancy ≥ 12 weeks.
  • Subject must meet all of the following criteria based on the centrally analyzed laboratory tests within 14 days prior to the first dose of study treatment. In case of multiple laboratory data within this period, the most recent data should be used to determine eligibility.
  • Hemoglobin (Hgb) ≥ 9 g/dL. NOTE: subject must not have received any growth factor or blood transfusions within 14 days prior to the hematology values obtained at screening. Subjects requiring transfusions to meet eligibility criteria are not eligible.
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

  • Platelets ≥ 100 x 109/L

  • Albumin ≥ 2.5 g/dL
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • 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 (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)

You CAN'T join if...

  • 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. Subject may have received treatment with herbal medications that have known anti-tumor activity >28 days prior to first dose of study treatment.
  • Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma unless the radiotherapy was completed >28 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.
  • 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) or a single dose of systemic corticosteroids are allowed.
  • Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
  • 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 mFOLFOX6.
  • Subject has known dihydropyrimidine dehydrogenase deficiency.
  • Subject has gastric outlet syndrome or persistent/recurrent vomiting.
  • Subject with recent gastric bleeding or symptomatic subjects with proven gastric ulcers that would 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 hepatitis C infection. 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 serology but negative hepatitis C virus (HCV) ribonucleic acid (RNA) test results are eligible.
  • Subject has an active autoimmune disease that has required systemic treatment within the past 2 years.
  • Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to start of study treatment.
  • 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)
  • Subject has known active central nervous system metastases and/or carcinomatous meningitis.
  • 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 before the start of study treatment.
  • Subject without complete recovery from a major surgical procedure ≤ 14 days before start of study treatment.
  • 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 comorbid 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.

Locations

  • UCSF-Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94158 United States
  • University of California Davis accepting new patients
    Sacramento California 95817 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Astellas Pharma Global Development, Inc.
ID
NCT03504397
Phase
Phase 3
Study Type
Interventional
Last Updated