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

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

The purpose of this study is to confirm the recommended phase 2 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 tumor markers and pharmacokinetics (PK) of zolbetuximab, Nab-P and GEM, and health-related quality of life (HRQoL).

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer; Metastatic Pancreatic Adenocarcinoma; Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: zolbetuximab; Drug: nab-paclitaxel; Drug: gemcitabine

Detailed Description

This study will have a safety lead in phase and a randomization phase.

• Study Type: Interventional
• Enrollment (Actual): 393
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Astellas Pharma Global Development; Phone Number: 800-888-7704; Email: Astellas.registration@astellas.com

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, NSW 2250
      • Site AU61008
    • Wollongong, New South Wales, Australia, HVGM+3C
      • Site AU61007
  • Victoria
    • Fitzroy, Victoria, Australia, 5XRF+WX
      • Site AU61005
    • Warrnambool, Victoria, Australia, VIC 3280
      • Site AU61006
• Brazil
  • Centro Passo Fundo, Brazil
    • Site BR55009
  • Rio Grande Do Sul, Brazil
    • Site BR55008
  • Santa Catarina, Brazil
    • Site BR55004
  • Sao Paulo, Brazil
    • Site BR55010
  • Sao Paulo, Brazil
    • Site BR55011
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Site BR55012
• China
  • Beijing, China
    • Site CN86001
  • Beijing, China
    • Site CN86014
  • Beijing, China
    • Site CN86008
  • Changchun, China
    • Site CN86026
  • Chongqing, China
    • Site CN86009
  • Guangdong, China
    • Site CN86004
  • Guangdong, China
    • Site CN86020
  • Guangzhou, China
    • Site CN86016
  • Harbin, China
    • Site CN86012
  • Hubei, China
    • Site CN86002
  • Jiangsu, China
    • Site CN86005
  • Jiangsu, China
    • Site CN86011
  • Jiangsu, China
    • Site CN86025
  • Shan XI, China
    • Site CN86024
  • Shandong, China
    • Site CN86023
  • Shanghai, China
    • Site CN86013
  • Shanghai, China
    • Site CN86006
  • Shanghai, China
    • Site CN86019
  • Tianjin, China
    • Site CN86007
  • Xinjiang, China
    • Site CN86022
  • Zhejiang, China
    • Site CN86003
  • Zhejiang, China
    • Site CN86018
  • Zhengzhou, China
    • Site CN86010
• France
  • Bayonne Cedex, France, 64109
    • Site FR33001
  • Bordeaux, France
    • Site FR33018
  • Grenoble, France
    • Site FR33002
  • Nice Cedex 2, France
    • Site FR33021
  • Pierre Benite, France
    • Site FR33023
  • Plerin, France, 22190
    • Site FR33014
  • Pringy Cedex, France, 74374
    • Site FR33005
  • Roche-Sur-Yon, France
    • Site FR33019
  • Strasbourg, France, 67000
    • Site FR33007
  • Besancon Cedex
    • Besancon, Besancon Cedex, France, 6XG7+42
      • Site FR33008
  • Brest Cedex
    • Brest, Brest Cedex, France, 9GV7+4G
      • Site FR33010
  • Cedex 5
    • Caen, Cedex 5, France, 14076
      • Site FR33015
  • Cedex 9
    • Chambray, Cedex 9, France, 37170
      • Site FR33006
  • Herblain Cedex
    • Herblain, Herblain Cedex, France, 44805
      • Site FR33012
  • Loir-et-Cher
    • La Chaussee Saint Victor, Loir-et-Cher, France, 41260
      • Site FR33016
  • Nancy Cedex
    • Nancy, Nancy Cedex, France, 54000
      • Site FR33009
  • Normandy
    • Rouen, Normandy, France, 76000
      • Site FR33017
  • Pessac
    • Aquitaine, Pessac, France, 33604
      • Site FR33003
  • Villejuif Cedex
    • Villejuif, Villejuif Cedex, France, 94805
      • Site FR33013
• Ireland
  • Dublin
    • Elm Park, Dublin, Ireland, D04 T6F4
      • Site IR35301
• Italy
  • Cremona, Italy, 26100
    • Site IT39002
  • Lombardia, Italy
    • Site IT39010
  • Milan, Italy, 20141
    • Site IT39003
  • Toscana, Italy
    • Site IT39014
  • Veneto, Italy
    • Site IT39008
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Site IT39006
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Site IT39004
• Japan
  • Fukuoka, Japan
    • Site JP81004
  • Osaka, Japan
    • Site JP81010
  • Wakayama, Japan
    • Site JP81009
  • Aichi
    • Nagoya, Aichi, Japan
      • Site JP81007
  • Chiba
    • Kashiwa, Chiba, Japan
      • Site JP81001
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Site JP81005
  • Kanagawa
    • Yokohama, Kanagawa, Japan
      • Site JP81006
  • Nara
    • Kashihara, Nara, Japan
      • Site JP81003
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Site JP81011
    • Chuo-ku, Tokyo, Japan
      • Site JP81012
    • Koto-ku, Tokyo, Japan
      • Site JP81014
    • Mitaka, Tokyo, Japan
      • Site JP81013
    • Shinjuku-ku, Tokyo, Japan
      • Site JP81002
  • Yamaguchi
    • Ube, Yamaguchi, Japan
      • Site JP81015
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Site KR82010
  • Gyeonggi-do, Korea, Republic of
    • Site KR82009
  • Jeollanam-do, Korea, Republic of
    • Site KR82011
  • Seoul, Korea, Republic of, 152-703
    • Site KR82007
  • Seoul, Korea, Republic of, 03080
    • Site KR82001
  • Seoul, Korea, Republic of, 120-752
    • Site KR82003
  • Seoul, Korea, Republic of, 138-736
    • Site KR82004
  • Seoul, Korea, Republic of, F3QP+76
    • Site KR82002
  • Seoul, Korea, Republic of, G234+36
    • Site KR82006
  • Gyeonggi-do
    • Seongnam-Si, Gyeonggi-do, Korea, Republic of, 013620
      • Site KR82005
    • Suwon-si, Gyeonggi-do, Korea, Republic of
      • Site KR82008
• Mexico
  • Distrito Federal, Mexico
    • Site MX52004
  • San Luis Potosi, Mexico
    • Site MX52003
  • Veracruz, Mexico
    • Site MX52005
• Spain
  • Barcelona, Spain, 08028
    • Site ES34010
  • Barcelona, Spain, 08036
    • Site ES34013
  • Barcelona, Spain, 08916
    • Site ES34007
  • Barcelona, Spain
    • Site ES34018
  • Barcelona, Spain
    • Site ES34021
  • Caceres, Spain, 10003
    • Site ES34014
  • Cordoba, Spain
    • Site ES34022
  • Lleida, Spain, 25198
    • Site ES34005
  • Madrid, Spain, 28027
    • Site ES34015
  • Madrid, Spain, 28033
    • Site ES34006
  • Madrid, Spain, 28034
    • Site ES34009
  • Malaga, Spain
    • Site ES34026
  • Santander, Spain
    • Site ES34024
  • Santiago de Compostela, Spain
    • Site ES34017
  • Barcelona
    • Llobregat, Barcelona, Spain, 08908
      • Site ES34004
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Site ES34003
• Taiwan
  • New Taipei City, Taiwan
    • Site TW88608
  • Taichung City, Taiwan, 5M5J+36
    • Site TW88602
  • Taipei City, Taiwan, 4G9C+W3
    • Site TW88601
  • Taipei City, Taiwan
    • Site TW88609
• Turkey
  • Ankara, Turkey
    • Site TR90004
  • Ankara, Turkey
    • Site TR90006
  • Diyarbakir, Turkey
    • Site TR90003
  • Istanbul, Turkey
    • Site TR90002
  • Konya, Turkey
    • Site TR90001
• United States
  • California
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Medical Group
    • Whittier, California, United States, 90603
      • TOI Clinical Research
  • Connecticut
    • Meriden, Connecticut, United States, 06451
      • Midstate Medical Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute
    • Miami, Florida, United States, 33176
      • Baptist Health
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Cancer Treatment Centers of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute (NCI)
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Health System
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • David C Pratt Cancer Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Cancer Institute
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • Lake Success, New York, United States, 11042
      • Northwell Health Cancer Institute
    • New York, New York, United States, 10022
      • Memorial Sloan-Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Washington
    • Gig Harbor, Washington, United States, 98335
      • MultiCare Regional Cancer Center - Gig Harbor
    • Olympia, Washington, United States, 98502
      • Vista Oncology
    • Seattle, Washington, United States, 98101
      • Virginia Mason

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

  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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: zolbetuximab +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.	Drug: zolbetuximab; Administered as an intravenous infusion.; Other Names: IMAB362; Drug: nab-paclitaxel; Administered as an intravenous infusion; Drug: gemcitabine; Administered as an intravenous infusion
Active Comparator: nab-paclitaxel + gemcitabine; 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.	Drug: nab-paclitaxel; Administered as an intravenous infusion; Drug: gemcitabine; Administered as an intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLT) - (safety lead in)	Incidence of dose limiting toxicities.	Up to 28 days
Overall Survival (OS)	OS is defined as the time from the date of randomization until the date of death from any cause.	Up to 65 months
Safety assessed by Adverse Events (AEs)	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.	Up to 65 months
Safety assessed by incidence of serious adverse events (SAE)	Adverse Event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.	Up to 65 months
Safety assessed by incidence of treatment emergent adverse events (TEAE)	Treatment Emergent Adverse Event (TEAE) is defined as any AE which starts, or worsens, after the first dose of study drug through 30 days after the last dose of study drug.	Up to 65 months
Number of participants with laboratory value abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant laboratory values.	Up to 65 months
Number of participants with vital sign abnormalities and /or adverse events (AEs)	Number of participants with potentially clinically significant vital sign values.	Up to 65 months
Number of participants with electrocardiograms (ECG) abnormalities and or adverse events	12-lead ECGs will be recorded. Prior to the ECG, participants should rest in supine position for 10 minutes. ECGs will be read and assessed locally.	Up to 65 months
Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events	Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.	Up to 65 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization until the date of radiological progressive disease (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by investigator evaluation or death from any cause, whichever is earliest.	Up to 65 months
Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1.	Up to 65 months
Number of anti-drug antibody (ADA) Positive Participants	Immunogenicity will be measured by the number of participants that are ADA positive.	Up to 65 months
Disease Control Rate (DCR)	DCR is defined as the proportion of participants who have best overall response of stable disease, complete response (CR) or partial response (PR) as assessed by investigator evaluation per RECIST 1.1	Up to 65 months
Duration Of Response (DOR)	DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation per RECIST 1.1 or date of death from any cause, whichever is earliest.	Up to 65 months
Change in CA (Cancer Antigen) 19-9	Change from baseline in serum CA19-9 will be assessed.	Baseline up to 65 months
PK of zolbetuximab: Concentration Immediately Prior to Dosing (Ctrough)	Ctrough will be derived from the PK serum samples collected.	Up to 65 months
PK of Nab-P: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf)	AUCinf will be derived from the PK plasma samples collected.	Up to 30 days
PK of Nab-P: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast)	AUClast will be derived from the PK plasma samples collected.	Up to 30 days
PK of Nab-P: Maximum Concentration (Cmax)	Cmax will be derived from the PK plasma samples collected.	Up to 30 days
PK of Nab-P: Time of Maximum Concentration (Tmax)	Tmax will be derived from the PK plasma samples collected.	Up to 30 days
PK of Nab-P: Terminal Elimination Half-life (T1/2)	T1/2 will be derived from the PK plasma samples collected.	Up to 30 days
PK of Nab-P: Clearance (CL)	CL will be derived from the PK plasma samples collected.	Up to 30 days
PK of Nab-P: Volume of Distribution During the Terminal Phase (Vz)	Vz will be derived from the PK plasma samples collected.	Up to 30 days
PK of gemcitabine: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf)	AUCinf will be derived from the PK plasma samples collected.	Up to 30 days
PK of gemcitabine: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast)	AUClast will be derived from the PK plasma samples collected.	Up to 30 days
PK of gemcitabine: Maximum Concentration (Cmax)	Cmax will be derived from the PK plasma samples collected.	Up to 30 days
PK of gemcitabine: Time of Maximum Concentration (Tmax)	Tmax will be derived from the PK plasma samples collected.	Up to 30 days
PK of gemcitabine: Terminal Elimination Half-life (T1/2)	T1/2 will be derived from the PK plasma samples collected.	Up to 30 days
PK of gemcitabine: Clearance (CL)	CL will be derived from the PK plasma samples collected.	Up to 30 days
PK of gemcitabine: Volume of Distribution During the Terminal Phase (Vz)	Vz will be derived from the PK plasma samples collected.	Up to 30 days
Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30)	The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Pancreatic Cancer Module (EORTC-QLQ-PAN-26)	EORTC-QLQ-PAN26 is a 26-item questionnaire that evaluates pancreatic cancer-specific symptoms such as pain, dietary changes, jaundice, altered bowel habits, and emotional problems. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Health Related Quality of Life (HRQoL) measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L)	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome consisting of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale for health status. Each domain comprises 5 severity levels (no problems, slight problems, moderate problems, severe problems, extreme problems). The general visual analog scale records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.	Up to 65 months
Health Related Quality of Life (HRQoL) measured by the Patient Global Impression of Change (PGIC) scale	The PGIC is a single-item questionnaire that asks participants to provide the overall self-assessment of change in their disease on a 7-point scale ranging from "very much worse" to "very much better" as compared to the participant starting the study treatment. Only PGIC questions assessing pain and overall status will be collected.	Up to 65 months
Health Related Quality of Life (HRQoL) measured by the Patient Global Impression of Severity (PGIS) Scale	The PGIS is a single-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week, with 1 as "None" and 4 as "Severe". Only PGIS questions assessing pain and overall status will be collected.	Up to 65 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: January 23, 2019
• First Submitted That Met QC Criteria: January 23, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: pancreatic cancer; metastatic pancreatic cancer; gemcitabine; IMAB362; zolbetuximab; nab-paclitaxel; metastatic pancreatic adenocarcinoma; CLDN 18.2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Gemcitabine
• Other Study ID Numbers: 8951-CL-5201; 2018-002551-15 (EudraCT Number); CTR20220914 (Registry Identifier: ChinaDrugTrials.org.cn)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No