Clinical Trials List
Protocol Number8951-CL-5201
NCT Number(ClinicalTrials.gov Identfier)NCT03816163
2019-04-01 - 2025-06-30
Phase II
Recruiting8
ICD-10C25.9
Malignant neoplasm of pancreas, unspecified
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9157.9
Malignant neoplasm of pancreas, part unspecified
A Phase 2, 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
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Trial Applicant
ICON Clinical Research Pte Ltd
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Sponsor
Astellas Pharma Global Development, Inc.
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Yu Lien Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yi-Ping Hung Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- 李癸汌 無
- Yun-Cheng Hsieh Division of Hematology & Oncology
- 姜乃榕 無
- San-Chi Chen Division of Hematology & Oncology
- Shao-Jung Hsu Digestive System Department
- Yee Chao Division of Hematology & Oncology
- Pei-Chang Lee Division of Hematology & Oncology
- Hung-Yuan Yu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 姜乃榕 Division of Hematology & Oncology
- Yan-Shen Shan Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Nai-Jung Chiang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
- Wen-Chi Chou Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Yung-Chia Kao 未分科
- Wen-Chi Shen Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- 吳教恩 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tsu-Yi Chao 無
- TSU-YI CHAO 無
- 莊博雅 無
- Wei-Hong Cheng 無
- HUI-WEN LIU 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Pancreatic Adenocarcinoma
Objectives
Primary Objective
● To confirm the recommended phase 2 dose (RP2D) of zolbetuximab in combination with
Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic
adenocarcinoma (Safety Lead-in Phase)
● To determine antitumor activity of zolbetuximab measured by the 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
Secondary Objectives
Key Secondary:
● To evaluate additional antitumor activities of zolbetuximab in combination with Nab-P +
GEM measured by PFS and ORR (Randomization Phase)
Secondary:
● To evaluate pharmacokinetics of Nab-P + GEM in combination with zolbetuximab
(Randomization Phase)
● To evaluate additional antitumor activities measured by disease control rate (DCR) and
duration of response (DOR) (Randomization Phase)
● To evaluate the change in serum CA19-9 (Randomization Phase)
● To evaluate pharmacokinetics and immunogenicity of zolbetuximab in combination with
Nab-P + GEM
Exploratory Objectives
● To evaluate potential genomic and/or other biomarkers that may correlate with treatment
outcome
Test Drug
Zolbetuximab (IMAB362)
Active Ingredient
Zolbetuximab
Dosage Form
IVT
Dosage
105mg
Endpoints
Primary Endpoints
● Confirm RP2D as assessed by DLTs (Safety Lead-in Phase)
● Safety and tolerability as measured by AEs, laboratory test results, vital signs, ECGs and
ECOG performance status.
● OS, defined as the time from the date of randomization until the date of death from any
cause
Secondary Endpoints
Key Secondary (Randomization):
● PFS, defined as the time from the date of randomization until the date of radiological PD
per RECIST 1.1 by local investigator evaluation, or death from any cause, whichever is
earliest
● ORR, defined as the proportion of subjects who have a best overall response of CR or PR
as assessed by local investigator evaluation per RECIST 1.1
Secondary:
● Pharmacokinetic parameters of zolbetuximab, Nab-P (measured as PTX) and GEM
(AUCinf, AUCinf [%extrap], AUClast, Cmax, Ctrough, tmax, t1/2, , tlast, CL, Vz, as appropriate)
● DCR, defined as the proportion of subjects who have a best overall response of CR, PR
or stable disease (SD) as assessed by local investigator evaluation per RECIST 1.1
● DOR, defined as the time from the date of the first response (CR/PR) until the date of PD
as assessed by local investigator evaluation per RECIST 1.1 or date of death from any
cause, whichever is earliest
● Serum CA19-9 change from baseline
● Immunogenicity of zolbetuximab as measured by the frequency of anti-drug antibody
(ADA) positive subjects
The primary and key secondary endpoints will be evaluated at the time of interim analysis.
All endpoints will be evaluated at primary analysis.
Exploratory Endpoints
Potential genomic and/or other exploratory biomarkers that may be correlated to treatment
outcome of zolbetuximab.
● Confirm RP2D as assessed by DLTs (Safety Lead-in Phase)
● Safety and tolerability as measured by AEs, laboratory test results, vital signs, ECGs and
ECOG performance status.
● OS, defined as the time from the date of randomization until the date of death from any
cause
Secondary Endpoints
Key Secondary (Randomization):
● PFS, defined as the time from the date of randomization until the date of radiological PD
per RECIST 1.1 by local investigator evaluation, or death from any cause, whichever is
earliest
● ORR, defined as the proportion of subjects who have a best overall response of CR or PR
as assessed by local investigator evaluation per RECIST 1.1
Secondary:
● Pharmacokinetic parameters of zolbetuximab, Nab-P (measured as PTX) and GEM
(AUCinf, AUCinf [%extrap], AUClast, Cmax, Ctrough, tmax, t1/2, , tlast, CL, Vz, as appropriate)
● DCR, defined as the proportion of subjects who have a best overall response of CR, PR
or stable disease (SD) as assessed by local investigator evaluation per RECIST 1.1
● DOR, defined as the time from the date of the first response (CR/PR) until the date of PD
as assessed by local investigator evaluation per RECIST 1.1 or date of death from any
cause, whichever is earliest
● Serum CA19-9 change from baseline
● Immunogenicity of zolbetuximab as measured by the frequency of anti-drug antibody
(ADA) positive subjects
The primary and key secondary endpoints will be evaluated at the time of interim analysis.
All endpoints will be evaluated at primary analysis.
Exploratory Endpoints
Potential genomic and/or other exploratory biomarkers that may be correlated to treatment
outcome of zolbetuximab.
Inclution Criteria
Subject is eligible for the study if all of the following apply:
General Criteria
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written
informed consent and privacy language as per national regulations (e.g., Health
Insurance Portability and Accountability Act Authorization for United States sites) must
be obtained from the subject or legally authorized representative prior to any studyrelated procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is considered an adult according to local regulation at the time of signing
informed consent.
3. Subject agrees not to participate in another interventional study while receiving study
drug in present study
4. A female subject is eligible to participate if she is not pregnant or lactating [see
Appendix 12.3 Contraception Requirements] and at least 1 of the following conditions
applies:
● Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3
Contraception Requirements]
OR
● WOCBP who agrees to follow the contraceptive guidance as defined in
[Appendix 12.3 Contraception Requirements] throughout the treatment period and
for at least 6 months after the final study drug administration.
5. 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.
6. Female subject must not donate ova starting at screening and throughout the study
period, and for 6 months after the final study drug administration.
7. A male subject with female partner(s) of child-bearing potential must agree to use
contraception as detailed in [Appendix 12.3 Contraception Requirements] during the
treatment period and for at least 6 months after the final study drug administration.
8. A male subject must not donate sperm during the treatment period and for at least 6
months after the final study drug administration.
9. 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.
Disease Specific Criteria
10. Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
11. Subjects must have metastatic pancreatic cancer that has not been previously treated with
chemotherapy.
● Prior treatment with 5-FU or GEM administered as a radiation sensitizer during
and up to 4 weeks after radiation therapy is allowed (if there is lingering toxicity,
then the sponsor should be consulted).
● If a subject received therapy in the adjuvant setting, tumor recurrence or disease
progression must have occurred at least 6 months after completing the last dose of
adjuvant therapy.
12. Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1
within 28 days prior to the first dose of study treatment. For subjects with only 1
measureable lesion and prior radiotherapy, the lesion must be outside the field of prior
radiotherapy or must have documented progression following radiation therapy.
13. Subject’s tumor sample has CLDN18.2 expression in ≥ 75% of tumor cells
demonstrating moderate to strong membranous staining as determined by central IHC
testing
Physical or Laboratory Findings
14. Subject has ECOG performance status of 0 or 1.
15. Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
16. 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 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 xULN 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)
Waivers to the inclusion criteria will NOT be allowed.
General Criteria
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written
informed consent and privacy language as per national regulations (e.g., Health
Insurance Portability and Accountability Act Authorization for United States sites) must
be obtained from the subject or legally authorized representative prior to any studyrelated procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is considered an adult according to local regulation at the time of signing
informed consent.
3. Subject agrees not to participate in another interventional study while receiving study
drug in present study
4. A female subject is eligible to participate if she is not pregnant or lactating [see
Appendix 12.3 Contraception Requirements] and at least 1 of the following conditions
applies:
● Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3
Contraception Requirements]
OR
● WOCBP who agrees to follow the contraceptive guidance as defined in
[Appendix 12.3 Contraception Requirements] throughout the treatment period and
for at least 6 months after the final study drug administration.
5. 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.
6. Female subject must not donate ova starting at screening and throughout the study
period, and for 6 months after the final study drug administration.
7. A male subject with female partner(s) of child-bearing potential must agree to use
contraception as detailed in [Appendix 12.3 Contraception Requirements] during the
treatment period and for at least 6 months after the final study drug administration.
8. A male subject must not donate sperm during the treatment period and for at least 6
months after the final study drug administration.
9. 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.
Disease Specific Criteria
10. Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
11. Subjects must have metastatic pancreatic cancer that has not been previously treated with
chemotherapy.
● Prior treatment with 5-FU or GEM administered as a radiation sensitizer during
and up to 4 weeks after radiation therapy is allowed (if there is lingering toxicity,
then the sponsor should be consulted).
● If a subject received therapy in the adjuvant setting, tumor recurrence or disease
progression must have occurred at least 6 months after completing the last dose of
adjuvant therapy.
12. Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1
within 28 days prior to the first dose of study treatment. For subjects with only 1
measureable lesion and prior radiotherapy, the lesion must be outside the field of prior
radiotherapy or must have documented progression following radiation therapy.
13. Subject’s tumor sample has CLDN18.2 expression in ≥ 75% of tumor cells
demonstrating moderate to strong membranous staining as determined by central IHC
testing
Physical or Laboratory Findings
14. Subject has ECOG performance status of 0 or 1.
15. Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
16. 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 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 xULN 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)
Waivers to the inclusion criteria will NOT be allowed.
Exclusion Criteria
Subject will be excluded from participation if any of the following apply:
Prohibited Treatment or Therapies
1. Subject has received other investigational treatment within 28 days prior to screening.
2. 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.
3. 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.
Medical History or Concurrent Disease
4. Subject has prior severe allergic reaction or intolerance to known ingredients of
zolbetuximab or other monoclonal antibody, including humanized or chimeric
antibodies.
5. Subject has known immediate or delayed hypersensitivity, intolerance or
contraindication to any component of study treatment.
6. 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.
7. Subject has a history of interstitial pneumonia or pulmonary fibrosis.
8. Subject has pleural effusion or ascites ≥ Grade 3 per CTCAE v 4.0.
9. Subject has an active autoimmune disease that has required systemic treatment in the
past 2 years
10. Subject has active infection requiring systemic therapy that has not completely resolved
per investigator judgment within 14 days prior to first dose of study treatment.
11. 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.)
12. Subject has known active or treated central nervous system metastases and/or
carcinomatous meningitis.
13. Subject has known peripheral sensory neuropathy ≥ Grade 2 per CTCAE v.4.0 unless the
absence of deep tendon reflexes is the sole neurological abnormality.
14. Subject has had a major surgical procedure ≤ 28 days prior to the first dose of study
drug.
15. Subject without complete recovery from a major surgical procedure ≤ 14 days prior to
the first dose of study treatment.
16. Psychiatric illness or social situations that would preclude study compliance per
investigator’s judgment.
17. Subject has another malignancy for which treatment is required per investigator’s clinical
judgment.
18. 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 in the opinion of the investigator.
Waivers to the exclusion criteria will NOT be allowed.
Prohibited Treatment or Therapies
1. Subject has received other investigational treatment within 28 days prior to screening.
2. 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.
3. 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.
Medical History or Concurrent Disease
4. Subject has prior severe allergic reaction or intolerance to known ingredients of
zolbetuximab or other monoclonal antibody, including humanized or chimeric
antibodies.
5. Subject has known immediate or delayed hypersensitivity, intolerance or
contraindication to any component of study treatment.
6. 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.
7. Subject has a history of interstitial pneumonia or pulmonary fibrosis.
8. Subject has pleural effusion or ascites ≥ Grade 3 per CTCAE v 4.0.
9. Subject has an active autoimmune disease that has required systemic treatment in the
past 2 years
10. Subject has active infection requiring systemic therapy that has not completely resolved
per investigator judgment within 14 days prior to first dose of study treatment.
11. 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.)
12. Subject has known active or treated central nervous system metastases and/or
carcinomatous meningitis.
13. Subject has known peripheral sensory neuropathy ≥ Grade 2 per CTCAE v.4.0 unless the
absence of deep tendon reflexes is the sole neurological abnormality.
14. Subject has had a major surgical procedure ≤ 28 days prior to the first dose of study
drug.
15. Subject without complete recovery from a major surgical procedure ≤ 14 days prior to
the first dose of study treatment.
16. Psychiatric illness or social situations that would preclude study compliance per
investigator’s judgment.
17. Subject has another malignancy for which treatment is required per investigator’s clinical
judgment.
18. 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 in the opinion of the investigator.
Waivers to the exclusion criteria will NOT be allowed.
The Estimated Number of Participants
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Taiwan
25 participants
-
Global
357 participants
