Informations générales (source: ClinicalTrials.gov)
A Phase 2, Open-Label, Randomized Study to Assess the Efficacy 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
Interventional
Phase 2
Astellas Pharma Global Development, Inc. (Voir sur ClinicalTrials)
mars 2019
août 2026
02 août 2025
Zolbetuximab is being studied as a treatment for people with pancreatic cancer. Most
people with pancreatic cancer have a protein called Claudin 18.2 (CLDN18.2) in their
tumor. Zolbetuximab is thought to work by attaching to CLDN 18.2 in their tumor. This
switches on the body's immune system to attack the tumor. Zolbetuximab is a potential
treatment for people with pancreatic cancer.
There is an unmet medical need to treat people with pancreatic cancer. This study will
help find the dose of zolbetuximab to be used with chemotherapy and provide more
information on this treatment in adults with metastatic pancreatic cancer. The study is
currently ongoing globally. People in this study will be treated with either zolbetuximab
and chemotherapy or chemotherapy by itself.
The study's main aims are to find a suitable dose of zolbetuximab to be used with
chemotherapy in the second part of this study, to check if zolbetuximab and chemotherapy
compared to chemotherapy by itself can improve the survival of people with pancreatic
cancer, and to check the safety of zolbetuximab when given with chemotherapy and how well
people cope with medical problems during the study.
Adults with metastatic pancreatic cancer can take part. Their cancer is metastatic, has
the CLDN18.2 marker in a tumor sample and has not previously been treated with
chemotherapy. Metastatic means the cancer has spread to other parts of the body. People
cannot take part are if they have recently had radiotherapy and have not recovered, need
to take medicines to suppress their immune system, have history of nervous system
metastases from their pancreatic cancer, or they have other active cancers that need
treatment. People who have a specific heart condition or infections also cannot take
part.
This study will be in 2 parts. Part 1 is called the Safety Lead-in Phase. Groups of
people will receive 1 of 2 different doses of zolbetuximab: a lower dose or a higher
dose, both together with chemotherapy. A medical expert panel will check the results and
decide the dose to use in Part 2.
Part 2 is called the Randomization Phase. People will be put in 1 of 2 groups by chance
and will be given different treatments either zolbetuximab and chemotherapy or
chemotherapy by itself. The chance of receiving zolbetuximab and chemotherapy is twice as
high as receiving chemotherapy by itself. In both parts of the study, zolbetuximab and
chemotherapy or chemotherapy by itself will be given through a vein. This is called an
infusion. Each treatment cycle is 4 weeks (28 days) long and people will have either 2
infusions of zolbetuximab and 3 infusions of chemotherapy or 3 infusions of chemotherapy
by itself during each treatment cycle. People will visit the clinic on certain days
during their treatment. The study doctors will check for any medical problems from
zolbetuximab. Also, people in the study will have a health check including blood tests.
On some visits they will also have scans to check for any changes in their cancer. Tumor
samples will be taken before treatment if a previous sample is not available. People will
have the option of giving a tumor sample after treatment has finished. People will visit
the clinic after they stop treatment. They will be asked about any medical problems and
will have a health check including blood tests. The number of visits and checks done at
each visit will depend on the health of each person and whether they completed their
treatment or not.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Michel DUCREUX | 26/04/2024 17:53:41 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Site FR33001 - 64109 - Bayonne Cedex - France | Contact (sur clinicalTrials) | ||||
| Site FR33002 - Grenoble - France | Contact (sur clinicalTrials) | ||||
| Site FR33003 - 33604 - Aquitaine - Pessac - France | Contact (sur clinicalTrials) | ||||
| Site FR33005 - 74374 - Pringy Cedex - France | Contact (sur clinicalTrials) | ||||
| Site FR33006 - 37170 - Chambray - Cedex 9 - France | Contact (sur clinicalTrials) | ||||
| Site FR33007 - 67000 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Site FR33008 - 6XG7+42 - Besancon - Besancon Cedex - France | Contact (sur clinicalTrials) | ||||
| Site FR33009 - 54000 - Nancy - Nancy Cedex - France | Contact (sur clinicalTrials) | ||||
| Site FR33010 - 9GV7+4G - Brest - Brest Cedex - France | Contact (sur clinicalTrials) | ||||
| Site FR33012 - 44805 - Herblain - Herblain Cedex - France | Contact (sur clinicalTrials) | ||||
| Site FR33013 - 94805 - Villejuif - Villejuif Cedex - France | Contact (sur clinicalTrials) | ||||
| Site FR33014 - 22190 - Plerin - France | Contact (sur clinicalTrials) | ||||
| Site FR33015 - 14076 - Caen - Cedex 5 - France | Contact (sur clinicalTrials) | ||||
| Site FR33016 - 41260 - La Chaussee Saint Victor - Loir-et-Cher - France | Contact (sur clinicalTrials) | ||||
| Site FR33017 - 76000 - Rouen - Normandy - France | Contact (sur clinicalTrials) | ||||
| Site FR33018 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| Site FR33019 - Roche-Sur-Yon - France | Contact (sur clinicalTrials) | ||||
| Site FR33021 - Nice Cedex 2 - France | Contact (sur clinicalTrials) | ||||
| Site FR33023 - Pierre Benite - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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)
- 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)
- 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.
1. 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.
2. Subjects with positive hepatitis C serology but negative hepatitis C virus RNA
test results are eligible.
3. 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.