A Study to Assess the Efficacy and Safety of 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
Pancreatic Cancer, Metastatic Pancreatic Cancer, Metastatic Pancreatic Adenocarcinoma
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring metastatic pancreatic cancer, IMAB362, nab-paclitaxel, gemcitabine, zolbetuximab, metastatic pancreatic adenocarcinoma, pancreatic cancer, CLDN 18.2
Eligibility Criteria
Inclusion Criteria:
A female subject is eligible to participate if she is not pregnant or lactating and at least 1 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 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 not donate ova starting at screening and throughout the study period, and for 6 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 6 months after the final study drug administration.
- A male subject must not donate sperm during the treatment period and for at least 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 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 adenocarcinoma 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 4 weeks after radiation therapy is allowed
- If a subject received adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the adjuvant therapy.
- Subjects whose disease progressed on prior treatment with Nab-P and GEM are not eligible.
- Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to randomization. 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 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 based on the laboratory tests that will be collected within 14 days prior to randomization. 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)
Exclusion Criteria:
- Subject has received other investigational treatment within 28 days prior to randomization.
- Subject has received radiotherapy for metastatic pancreatic adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
- Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. 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), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
- 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. NOTE: Screening for these infections should be conducted per local requirements.
- 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 hepatitis C serology but negative hepatitis C virus RNA test results are eligible.
- Subjects treated for hepatitis C with undetectable viral load 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 3 months prior to randomization.
- Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 7 days prior to randomization.
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 randomization;
- 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 randomization.)
- Subject has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma.
- 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 randomization.
- Subject without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
- 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.
Sites / Locations
- Cancer Treatment Centers of Phoenix
- St. Joseph Heritage Medical GroupRecruiting
- Hoag HospitalRecruiting
- UCLA Hematology Oncology
- TOI Clinical researchRecruiting
- Midstate Medical CenterRecruiting
- Lynn Cancer InstituteRecruiting
- Baptist HealthRecruiting
- Cancer Treatment Centers of Atlanta
- University of Illinois at ChicagoRecruiting
- The University of Chicago
- Cancer Treatment Centers of America, Chicago
- PMG Research of McFarland Clinic
- Holden Comprehensive Cancer CenterRecruiting
- University of Kansas Cancer Center
- Norton Cancer Institute (NCI)Recruiting
- Our Lady of the Lake
- Ochsner Health System
- David C Pratt Cancer Center
- St Vincent's Frontier Cancer CenterRecruiting
- Memorial Sloan Kettering Basking RidgeRecruiting
- Memorial Sloan Kettering MonmouthRecruiting
- Memorial Sloan Kettering BergenRecruiting
- Roswell Park Cancer InstituteRecruiting
- Memorial Sloan Kettering CommackRecruiting
- Memorial Sloan Kettering WestchesterRecruiting
- Northwell Health Cancer Institute
- Memorial Sloan-Kettering Cancer CenterRecruiting
- Memorial Sloan Kettering NassauRecruiting
- Novant Health Presbyterian Medical CenterRecruiting
- Novant HealthRecruiting
- Mercy Clinic Oklahoma Communities, Inc
- Cancer Treatment Centers of America at Eastern Regional Medical Center
- Oncology Consultants PA
- Houston Methodist HospitalRecruiting
- Scott and White Memorial Hospital
- Utah Cancer SpecialistsRecruiting
- Inova Dwight and Martha ScharRecruiting
- MultiCare Regional Cancer Center - Gig HarborRecruiting
- Vista OncologyRecruiting
- Virginia MasonRecruiting
- Site AU61008Recruiting
- Site AU61007Recruiting
- Site AU61002
- Site AU61005Recruiting
- Site AU61006Recruiting
- Site BR55003Recruiting
- Site BR55002Recruiting
- Site BR55008Recruiting
- Site BR55004Recruiting
- Site BR55001Recruiting
- Site BR55006Recruiting
- Site CN86001Recruiting
- Site CN86008Recruiting
- Site CN86014Recruiting
- Site CN86026Recruiting
- Site CN86009Recruiting
- Site CN86004Recruiting
- Site CN86020Recruiting
- Site CN86016Recruiting
- Site CN86012Recruiting
- Site CN86002Recruiting
- Site CN86005Recruiting
- Site CN86011Recruiting
- Site CN86025Recruiting
- Site CN86024Recruiting
- Site CN86023Recruiting
- Site CN86006Recruiting
- Site CN86013Recruiting
- Site CN86019Recruiting
- Site CN86017Recruiting
- Site CN86007Recruiting
- Site CN86022Recruiting
- Site CN86003Recruiting
- Site CN86018Recruiting
- Site CN86010Recruiting
- Site FR33008Recruiting
- Site FR33010Recruiting
- Site FR33004
- Site FR33015Recruiting
- Site FR33006Recruiting
- Site FR33011Recruiting
- Site FR33012Recruiting
- Site FR33016Recruiting
- Site FR33009Recruiting
- Site FR33017Recruiting
- Site FR33003Recruiting
- Site FR33013Recruiting
- Site FR33001Recruiting
- Site FR33018Recruiting
- Site FR33002Recruiting
- Site FR33020Recruiting
- Site FR33021Recruiting
- Site FR33023Recruiting
- Site FR33014Recruiting
- Site FR33005Recruiting
- Site FR33019Recruiting
- Site FR33007Recruiting
- Site IR35301Recruiting
- Site IE35303Recruiting
- Site IT39006Recruiting
- Site IT39004Recruiting
- Site IT39009Recruiting
- Site IT39015Recruiting
- Site IT39002Recruiting
- Site IT39012Recruiting
- Site IT39010Recruiting
- Site IT39003Recruiting
- Site IT39014Recruiting
- Site IT39008Recruiting
- Site JP81007Recruiting
- Site JP81001Recruiting
- Site JP81005Recruiting
- Site JP81006Recruiting
- Site JP81003Recruiting
- Site JP81008Recruiting
- Site JP81011Recruiting
- Site JP81012Recruiting
- Site JP81014Recruiting
- Site JP81013Recruiting
- Site JP81002Recruiting
- Site JP81015Recruiting
- Site JP81004Recruiting
- Site JP81010
- Site JP81009Recruiting
- Site KR82005Recruiting
- Site KR82008Recruiting
- Site KR82010Recruiting
- Site KR82009Recruiting
- Site KR82011Recruiting
- Site KR82001Recruiting
- Site KR82003Recruiting
- Site KR82004Recruiting
- Site KR82007Recruiting
- Site KR82002Recruiting
- Site KR82006Recruiting
- Site MX52004Recruiting
- Site MX52003Recruiting
- Site MX52005Recruiting
- Site ES34004Recruiting
- Site ES34001Recruiting
- Site ES34011
- Site ES34003Recruiting
- Site ES34010Recruiting
- Site ES34013Recruiting
- Site ES34007Recruiting
- Site ES34018Recruiting
- Site ES34021Recruiting
- Site ES34014Recruiting
- Site ES34025Recruiting
- Site ES34022Recruiting
- Site ES34002Recruiting
- Site ES34005Recruiting
- Site ES34015
- Site ES34016Recruiting
- Site ES34006Recruiting
- Site ES34009Recruiting
- Site ES34012
- Site ES34008Recruiting
- Site ES34020Recruiting
- Site ES34026Recruiting
- Site ES34024Recruiting
- Site ES34017Recruiting
- Site TW88604Recruiting
- Site TW88606
- Site TW88607Recruiting
- Site TW88608Recruiting
- Site TW88602Recruiting
- Site TW88603
- Site TW88605
- Site TW88601Recruiting
- Site TW88609Recruiting
- Site TR90004Recruiting
- Site TR90006Recruiting
- Site TR90003Recruiting
- Site TR90002Recruiting
- Site TR90005Recruiting
- Site TR90001Recruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
zolbetuximab +nab-paclitaxel + gemcitabine
nab-paclitaxel + gemcitabine
Participants will be treated with zolbetuximab in combination with nab-paclitaxel and gemcitabine for the phase 1 portion of the study to establish the recommended dose of zolbetuximab for the phase 2 portion. In the phase 2 portion, the participants will be treated with zolbetuximab at dose determined by the phase 1 portion of the study in combination with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.
Participants will be treated with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.