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Astellas 8951-CL-5201: A phase II, open-label, randomized study to assess the antitumor activity and safety of zolbetuximab (IMAB362) in combination with nab-paclitaxel and gemcitabine (Nab-P + GEM) as first-line treatment in subjects with claudin 18.2 (CLDN18.2) positive, metastatic pancreatic adenocarcinoma

Description

The purpose of this study is to confirm the recommended phase II dose (RP2D) of zolbetuximab in combination with Nab-P + GEM, determine overall survival and assess the safety and tolerability of the combination treatment.

This study will also evaluate other anti-tumor effects, tumor markers and pharmacokinetics (PK) of zolbetuximab, Nab-P and GEM.

Status

Accepting new patients

Primary Study Objective(s)

The primary objectives of this study are to:

  • To confirm the recommended phase II dose (RP2D) of zolbetuximab in combination with Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Safety Leadin Phase)
  • To determine antitumor activity of zolbetuximab measured by the overall survival (OS) in combination with Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Randomization Phase)
  • To assess the safety and tolerability of zolbetuximab in combination with Nab-P + GEM

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who meet these criteria:

  • A female subject is eligible to participate if she is not pregnant or lactating and at least one of the following conditions applies:
    • Not a woman of childbearing potential (WOCBP), or
    • WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least six months after the final study drug administration
  • Female subject must agree not to breastfeed starting at screening and throughout the study period, and for six months after the final study drug administration.
  • Female subject must not donate ova starting at screening and throughout the study period, and for six months after the final study drug administration.
  • A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least six months after the final study drug administration.
  • A male subject must not donate sperm during the treatment period and for at least six 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 six months after the final study drug administration.
  • Subject agrees not to participate in other interventional studies while receiving study drug in present study.
  • Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
  • Subjects must have metastatic pancreatic cancer that has not been previously treated with chemotherapy.
    • Prior treatment with fluorouracil (5-FU) or GEM administered as a radiation sensitizer during and up to four weeks after radiation therapy is allowed.
    • If a subject received therapy in the adjuvant setting, tumor recurrence or disease progression must have occurred at least six months after completing the last dose of adjuvant therapy.
  • Subject has a measurable lesion(s) on at least one metastatic site based on RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only one 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 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing
  • Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 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 drug (In case of multiple laboratory data within this period, the most recent data should be used):
    • Hemoglobin ≥ 9 g/dl (no transfusion within 14 days of start of study treatment)
    • Absolute neutrophil count ≥ 1.5 x 10^9/L
    • Platelets ≥ 100 x 10^9/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/min
    • Prothrombin time/international normalized ratio (INR) and partial thromboplastin time ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)

Excluding patients who meet these criteria:

  • Subject has received other investigational treatment within 28 days prior to screening.
  • Subject has received radiotherapy for metastatic pancreatic adenocarcinoma within 28 days prior to the first dose of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases ≥ 14 days prior to first dose of study treatment and has recovered from all acute toxicities is eligible.
  • Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject 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 corticosteriods is eligible.
  • Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies.
  • Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
  • Subject has a known history of a positive test for human immunodeficiency virus infection or known active Hepatitis B (positive HBs antigen [Ag]) or Hepatitis C infection. For subjects who are negative for HBs Ag, but Hepatitis B core antibody positive, a Hepatitis B virus DNA test will be performed and if positive, the subject will be excluded. Subjects with positive serology but negative Hepatitis C virus RNA test results are eligible.
  • Subject has a history of interstitial pneumonia or pulmonary fibrosis.
  • Subject has pleural effusion or ascites ≥ Grade 3.
  • Subject has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to first dose 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, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to administration of first dose of study treatment;
    • History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
    • QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects;
    • Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible.)
  • Subject has known active or treated central nervous system metastases and/or carcinomatous meningitis.
  • Subject has known peripheral sensory neuropathy ≥ Grade 2 unless the absence of deep tendon reflexes is the sole neurological abnormality.
  • Subject has had a major surgical procedure ≤ 28 days prior to the first dose of study drug.
  • Subject without complete recovery from a major surgical procedure ≤ 14 days prior to the first dose of study treatment.
  • 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 co-morbid 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.