Summary

for people ages 18 years and up (full criteria)
at UCLA
study started
estimated completion

Description

Summary

The purpose of this study is to determine the Objective Response Rate (ORR) of zolbetuzimab as a single agent as assessed by an independent central reader. This study will also assess the ORR and Progression Free Survival (PFS) of zolbetuximab in combination with mFOLFOX6, assess the safety and tolerability, assess the effects on CLDN18.2 expression and assess the immunogenicity and immunomodulatory effects of zolbetuximab as a single agent and in combination with mFOLFOX6. This study will also evaluate the pharmacokinetics (PK) of zolbetuximab, oxaliplatin and fluorouracil (5-FU), evaluate health-Related Quality of Life (HRQoL), evaluate the Disease Control Rate (DCR), Duration of Response (DOR), PFS and Overall Survival (OS) of zolbetuximab as a single agent.

Official Title

A Phase 2 Study of Zolbetuximab (IMAB362) as Monotherapy or in Combination With mFOLFOX6 in Subjects With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma Whose Tumors Have High or Intermediate Claudin (CLDN) 18.2 Expression

Details

This is a study to assess the antitumor activity of zolbetuximab, an Immunoglobulin (IgG1) chimeric monoclonal antibody directed against CLDN18.2, in subjects with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors have high or intermediate CLDN18.2 expression. For each cohort, the study consists of the following periods: pre-screening; screening; treatment; and follow-up for disease progression. In addition, there will be a survival follow-up period for Cohort 1 subjects only.

Keywords

Pharmacokinetics of Zolbetuximab Gastric Cancer Gastro-esophageal Junction (GEJ) Cancer Pharmacokinetics of Oxaliplatin Pharmacokinetics of Fluorouracil Bolus (5-FU) zolbetuximab oxaliplatin fluorouracil claudiximab IMAB362 Gastro-Esophageal Junction cancer Adenocarcinoma Stomach Neoplasms Antibodies, Monoclonal leucovorin

Eligibility

You can join if…

Open to people ages 18 years and up

  • Female subject eligible to participate if she is not pregnant 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 gastric or GEJ adenocarcinoma.
  • Subject has radiographically-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 sample has CLDN18.2 expression (defined as moderate to strong membranous staining by central IHC testing) as follows:
  • Cohorts 1A and 2: CLDN18.2 high expression (≥ 75% of tumor cells)
  • Cohort 1B: CLDN18.2 high or intermediate expression (≥ 50% of tumor cells)
  • Cohorts 1A and 1B Only:
  • Subject has disease progression on or after at least 2 prior regimens for their advanced disease, including fluoropyrimidine and platinum-containing chemotherapy, and if appropriate, HER2/neu-targeted therapy.
  • Cohort 2 Only:
  • Subject has not received prior systemic anti-cancer therapy for their advanced disease (subject may have received neoadjuvant and/or fluorouracil-containing adjuvant chemotherapy as long as it has been completed ≥ 6 months before the first dose of study treatment).
  • Subject has a gastric or GEJ tumor that is HER2-negative as determined by local or central testing.
  • Cohorts 1A and 2:
  • Subject must have an additional available tumor specimen collected within 3 months prior to the first dose of study treatment.
  • Subject is an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the screening period (if applicable) and treatment period.
  • Subject agrees not to participate in another interventional study while on treatment.
  • Subject has ECOG performance status 0 to 1.
  • Subject has predicted life expectancy ≥ 12 weeks.
  • Subject must meet all of the following criteria on the laboratory tests that will be analyzed centrally 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.
  • Hemoglobin (Hgb) ≥ 9 g/dL (no transfusion within 7 days of start of study treatment)
  • 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 (≤ 5 x ULN if liver metastases are present)
  • Estimated creatinine clearance ≥ 30 mL
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for patients receiving anticoagulation therapy)

You CAN'T join if...

  • Subject has had 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 or contraindication to any component of study treatment.
  • Subject has received other investigational agents or devices concurrently or within 28 days prior to first dose of study treatment.
  • Subject has received systemic immunosuppressive therapy, including systemic corticosteroids 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 gastric outlet syndrome or persistent recurrent vomiting.
  • Subject with recent gastric bleeding or symptomatic subjects with proven gastric ulcers that would preclude the subject from participation.
  • Subject has known active central nervous system metastases and/or carcinomatous meningitis.
  • 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 [HBsAg]) or hepatitis C infection. Subjects who are negative for HBsAg, but hepatitis B core antibody positive, will have a hepatitis B DNA test performed and if positive will be excluded. Subjects with positive serology, but negative hepatitis C virus RNA test results, are eligible.
  • Subject has had within 6 months prior to first dose of study treatment any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure.
  • Subject has active infection requiring systemic therapy.
  • Subject has active autoimmune disease that has required systemic treatment in the past 2 years.
  • Subject has a clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this study or make the subject unsuitable for study participation.
  • Subject has psychiatric illness or social situations that would preclude study compliance.
  • Subject has had a major surgical procedure ≤ 28 days before start of study treatment.
  • Subject without complete recovery from a major surgical procedure ≤ 14 days before start of study treatment.
  • Subject has had radiotherapy ≤ 14 days (Cohort 1) and ≤ 28 days (Cohort 2) 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 another past or active malignancy, which is likely to require treatment.
  • Cohort 2 Only, subject has any of the following:
  • Prior severe allergic reaction or intolerance to any component of mFOLFOX6 chemotherapeutics in this study
  • Known dihydropyrimidine dehydrogenase deficiency
  • Known peripheral neuropathy > Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the subject ineligible).
  • Sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if present, should be stable or improving.
  • History of clinically significant ventricular arrhymias (i.e. sustained ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)
  • QTc interval >450 msec for male subjects; QTc interval >470 for female subjects
  • History or family history of congenital long QT syndrome
  • Cardiac arrhymias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible)

Locations

  • UCLA Medical Center accepting new patients
    Santa Monica California 90404 United States
  • The Angeles Clinic and Research Institute accepting new patients
    Los Angeles California 90025 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Astellas Pharma Global Development, Inc.
ID
NCT03505320
Phase
Phase 2
Study Type
Interventional
Last Updated