A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction (GEJ) Cancer (Spotlight)

April 15, 2024 updated by: Astellas Pharma Global Development, Inc.

A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

A study of zolbetuximab (IMAB362) plus mFOLFOX6 versus placebo plus mFOLFOX6 in subjects with Claudin 18.2 positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Why is this study being done? SPOTLIGHT is a new clinical study for adult patients who have any of: - advanced unresectable gastric or GEJ cancer - metastatic gastric or GEJ cancer. These types of cancers have a unique set of proteins (called Claudin 18.2). We may be able to use a treatment that targets the proteins to kill the cancer cells. For patients with one of the types of cancer listed above, mFOLFOX6 (a combination of three chemotherapies known as Oxaliplatin, Leucovorin, and Fluorouracil) is a current treatment option. This study is testing an experimental medicine called zolbetuximab (IMAB362). Zolbetuximab attaches itself to Claudin 18.2 on the cancer cells causing cancer cell death. Patients will be assigned to one of two groups by chance and given either: - zolbetuximab with mFOLFOX6; or - a placebo with mFOLFOX6. A placebo is a treatment that looks like the experimental medicine, but contains no medicine. The goal of the study is to find out if zolbetuximab with mFOLFOX6 helps patients to live longer by stopping the cancer from getting worse.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The study consists of the following periods: screening; treatment; post-treatment follow up, safety follow up, long term and survival follow-up.

Study Type

Interventional

Enrollment (Actual)

566

Phase

  • Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Kogarah, Australia, 2217
        • Site AU61007
    • Queensland
      • Douglas, Queensland, Australia, 4814
        • Site AU61002
      • Tugun, Queensland, Australia, 4224
        • Site AU61011
    • South Australia
      • Adelaide, South Australia, Australia, 5011
        • Site AU61008
    • Victoria
      • East Bentleigh, Victoria, Australia, 3165
        • Site AU61006
  • Belgium
      • Brugge, Belgium, 8310
        • Site BE32005
      • Brussels, Belgium, 1000
        • Site BE32004
      • Charleroi, Belgium, 6000
        • Site BE32011
      • Haine-Saint-Paul, Belgium, 7100
        • Site BE32010
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • Site BE32007
    • Bruxelles-Capitale, Région De
      • Bruxelles, Bruxelles-Capitale, Région De, Belgium, 1200
        • Site BE32001
    • Hainaut
      • Mons, Hainaut, Belgium, 7000
        • Site BE32008
    • Liege
      • Bruxelles, Liege, Belgium, 1050
        • Site BE32002
    • Oost-Vlaanderen
      • Gent, Oost-Vlaanderen, Belgium, 9000
        • Site BE32012
    • Vlaams Brabant
      • Leuven, Vlaams Brabant, Belgium, 3000
        • Site BE32006
  • Brazil
      • Belo Horizonte, Brazil, 30130-090
        • Site BR55017
      • Passo Fundo, Brazil, 99010-260
        • Site BR55016
      • Rio de Janeiro, Brazil, 22793-080
        • Site BR55015
      • Santa Catarina, Brazil, 88501-003
        • Site BR55018
      • São Paulo, Brazil, 01509-900
        • Site BR55009
      • São Paulo, Brazil, 08270-070
        • Site BR55004
    • Distrito Federal
      • Brasília, Distrito Federal, Brazil, 70200-730
        • Site BR55010
    • Rio Grande Do Sul
      • Lajeado, Rio Grande Do Sul, Brazil, 95900000
        • Site BR55006
    • Santa Catarina
      • Itajai, Santa Catarina, Brazil, 88301-220
        • Site BR55002
    • Sao Paulo
      • Santo Andre, Sao Paulo, Brazil, 09060-650
        • Site BR55003
      • Sao Jose do Rio Preto, Sao Paulo, Brazil, 15090-000
        • Site BR55005
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Site BR55007
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Site CA15005
    • New Brunswick
      • Saint-John, New Brunswick, Canada, E2L 4L4
        • Site CA15009
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X5
        • Site CA15011
    • Quebec
      • Montreal, Quebec, Canada, H3T 1M5
        • Site CA15002
      • Montreal, Quebec, Canada, H4A 3J1
        • Site CA15008
  • Chile
      • Providencia, Chile, 7520378
        • Site CL56008
      • Santiago, Chile, 8330032
        • Site CL56005
      • Valdivia, Chile, 5090000
        • Site CL56007
    • Santiago
      • Providencia, Santiago, Chile, 7500921
        • Site CL56003
  • China
      • Beijing, China, 100030
        • Site CN86009
      • Beijing, China, 100071
        • Site CN86002
      • Hefei, China, 230022
        • Site CN86005
      • Xiamen, China
        • Site CN86001
      • Zhengzhou, China, 450000
        • Site CN86008
    • Heilongjiang
      • Haerbin, Heilongjiang, China, 150081
        • Site CN86003
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • Site CN86006
    • Zhejiang
      • Hangzhou Shi, Zhejiang, China, 310003
        • Site CN86004
  • Colombia
      • Cali, Colombia
        • Site CO57001
      • Medellin, Colombia, 0574
        • Site CO57002
    • Antioquia
      • Medellín, Antioquia, Colombia, 574
        • Site CO57006
    • Córdoba
      • Monteria, Córdoba, Colombia, 230002
        • Site CO57007
    • DC
      • Bogota, DC, Colombia, 110231
        • Site CO57009
    • Valle
      • Cali, Valle, Colombia
        • Site CO57005
  • France
      • Creteil, France, 94000
        • Site FR33103
      • Nice Cedex 2, France, 06189
        • Site FR33007
      • Saint Priest en Jarez, France, 42270
        • Site FR33104
    • Bourgogne
      • Dijon, Bourgogne, France, 21079
        • Site FR33009
    • Bretagne
      • Brest Cedex, Bretagne, France, 29609
        • Site FR33010
      • Rennes, Bretagne, France, 35042
        • Site FR33001
    • Franche-Comte
      • Besancon cedex, Franche-Comte, France, 25033
        • Site FR33008
    • Languedoc-Roussillon
      • Montpellier Cedex 5, Languedoc-Roussillon, France, 34298
        • Site FR33011
    • Paris
      • Paris cedex, Paris, France, 75970
        • Site FR33002
    • Pays-de-la-Loire
      • St Herblain, Pays-de-la-Loire, France, 44805
        • Site FR33101
    • Provence-Alpes-Côte-d'Azur
      • Nice, Provence-Alpes-Côte-d'Azur, France, 06200
        • Site FR33005
    • Rhone
      • Lyon, Rhone, France, 69008
        • Site FR33003
    • Vienne
      • Poitiers, Vienne, France, 86021
        • Site FR33006
  • Germany
      • Berlin, Germany, 13125
        • Site DE49012
      • Berlin, Germany, 13353
        • Site DE49011
      • Dresden, Germany, 1067
        • Site DE49018
      • Heilbronn, Germany, 74078
        • Site DE49019
    • Bavaria
      • Munich, Bavaria, Germany, 81377
        • Site DE49008
    • Bayern
      • Munchen, Bayern, Germany, 81925
        • Site DE49007
    • Rheinland-Pfalz
      • Mainz, Rheinland-Pfalz, Germany, 55101
        • Site DE49002
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Site DE49010
      • Leipzig, Sachsen, Germany, 04103
        • Site DE49004
    • Sachsen-Anhalt
      • Halle, Sachsen-Anhalt, Germany, 06108
        • Site DE49021
      • Magdeburg, Sachsen-Anhalt, Germany, 39104
        • Site DE49015
  • Israel
      • HaDarom, Israel, 7030000
        • Site IL97210
      • Haifa, Israel, 3109601
        • Site IL97201
      • Holon, Israel, 58100
        • Site IL97209
      • Jerusalem, Israel, 91031
        • Site IL97202
      • Tel Aviv, Israel, 64239
        • Site IL97203
    • HaMerkaz
      • Kfar Saba, HaMerkaz, Israel, 44281
        • Site IL97206
  • Italy
      • Ancona, Italy, 60126
        • Site IT39013
      • Bergamo, Italy, 24127
        • Site IT39004
      • Cremona, Italy, 26100
        • Site IT39009
      • Milano, Italy, 20132
        • Site IT39006
      • Milano, Italy, 20141
        • Site IT39008
      • Modena, Italy, 41124
        • Site IT39021
      • Padova, Italy, 35128
        • Site IT39016
      • Parma, Italy, 43126
        • Site IT39012
      • Perugia, Italy, 05100
        • Site IT39018
      • Piacenza, Italy, 29100
        • Site IT39003
      • Pisa, Italy, 56126
        • Site IT39019
      • Reggio Emilia, Italy, 42123
        • Site IT39022
      • Roma, Italy, 00128
        • Site IT39015
      • Terni, Italy, 5100
        • Site IT39026
      • Turin TO, Italy, 5-10126
        • Site IT39024
    • Forli
      • Meldola, Forli, Italy, 47014
        • Site IT39011
    • Lombardia
      • Monza, Lombardia, Italy, 20052
        • Site IT39020
    • VI
      • Vicenza, VI, Italy, 36100
        • Site IT39023
  • Japan
      • Fukuoka, Japan
        • Site JP81005
      • Osaka, Japan
        • Site JP81004
      • Osaka, Japan
        • Site JP81011
    • Aichi
      • Nagoya, Aichi, Japan
        • Site JP81009
    • Chiba
      • Kashiwa, Chiba, Japan
        • Site JP81003
    • Ehime
      • Matsuyama, Ehime, Japan
        • Site JP81002
    • Hokkaido
      • Sapporo, Hokkaido, Japan
        • Site JP81007
    • Hyogo
      • Kobe, Hyogo, Japan
        • Site JP81014
    • Osaka
      • Suita, Osaka, Japan
        • Site JP81001
    • Saitama
      • Hidaka, Saitama, Japan
        • Site JP81015
      • Kitaadachi-gun, Saitama, Japan
        • Site JP81010
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan
        • Site JP81012
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan
        • Site JP81013
      • Chuo-ku, Tokyo, Japan
        • Site JP81006
      • Koto-ku, Tokyo, Japan
        • Site JP81008
  • Korea, Republic of
      • Incheon, Korea, Republic of, 21556
        • Site KR82008
      • Seoul, Korea, Republic of, 03080
        • Site KR82003
      • Seoul, Korea, Republic of, 05505
        • Site KR82005
      • Seoul, Korea, Republic of, 152-703
        • Site KR82007
      • Seoul, Korea, Republic of, 6591
        • Site KR82006
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
        • Site KR82002
    • Gyeonggido [Kyonggi-do]
      • Suwon-si, Gyeonggido [Kyonggi-do], Korea, Republic of, 16247
        • Site KR82009
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
        • Site KR82004
  • Mexico
      • Aguascalientes, Mexico, 20230
        • Site MX52001
      • Distrito Federal, Mexico, 06720
        • Site MX52003
      • Jalisco, Mexico, 45030
        • Site MX52009
      • Oaxaca, Mexico
        • Site MX52004
      • San Luis De Potosi, Mexico, 78250
        • Site MX52008
    • Distrito Federal
      • Ciudad de México, Distrito Federal, Mexico, 3100
        • Site MX52007
      • Mexico, Distrito Federal, Mexico, 06760
        • Site MX52002
    • Veracruz
      • Veracruz, Ver, Veracruz, Mexico, 91900
        • Site MX52010
  • Peru
      • Arequipa, Peru, 4001
        • Site PE51003
      • Lima, Peru, 15036
        • Site PE51005
      • Lima, Peru, 15072
        • Site PE51006
      • Lima, Peru, L27
        • Site PE51001
    • Lima
      • San Isidro, Lima, Peru, L27
        • Site PE51004
  • Poland
      • Warszawa, Poland, 02-781
        • Site PL48009
    • Lubuskie
      • Lublin, Lubuskie, Poland, 20-090
        • Site PL48004
    • Mazowieckie
      • Ostroleka, Mazowieckie, Poland, 07-410
        • Site PL48007
      • Wieliszew, Mazowieckie, Poland, 05-135
        • Site PL48005
    • Podkarpackie
      • Brzozow, Podkarpackie, Poland, 36-20
        • Site PL48002
  • Spain
      • Barcelona, Spain, 08003
        • Site ES34005
      • Barcelona, Spain, 08025
        • Site ES34016
      • Barcelona, Spain, 08035
        • Site ES34015
      • Burgos, Spain, 09006
        • Site ES34019
      • Madrid, Spain, 28007
        • Site ES34008
      • Madrid, Spain, 28033
        • Site ES34017
      • Madrid, Spain, 28034
        • Site ES34004
      • Murcia, Spain, 30120
        • Site ES34003
      • Sevilla, Spain, 41009
        • Site ES34018
      • Zaragoza, Spain, 50009
        • Site ES34006
    • Barcelona
      • Badalona, Barcelona, Spain, 08028
        • Site ES34013
    • Castilla Y Leon
      • Avila, Castilla Y Leon, Spain, 05004
        • Site ES34010
    • Madrid
      • Alcorcon, Madrid, Spain, 28925
        • Site ES34011
  • Taiwan
      • Kaohsiung, Taiwan, 80756
        • Site TW88608
      • Kaohsiung, Taiwan, 833
        • Site TW88604
      • Taichung, Taiwan, 404
        • Site TW88603
      • Tainan, Taiwan, 704
        • Site TW88607
      • Taipei, Taiwan, 10002
        • Site TW88606
      • Taipei, Taiwan, 112
        • Site TW88601
    • Taoyuan
      • Kwei-Shan, Taoyuan, Taiwan, 333
        • Site TW88605
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Site GB44103
      • Coventry, United Kingdom, CV2 2DX
        • Site GB44009
      • Dundee, United Kingdom, DD2 4BF
        • Site GB44104
      • Leeds, United Kingdom, LS7 9TF
        • Site GB44008
      • London, United Kingdom, NW1 2PG
        • Site GB44002
      • London, United Kingdom, W1G 6AD
        • Site GB44004
      • Manchester, United Kingdom, M20 4BX
        • Site GB44001
    • Aberdeenshire
      • Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZN
        • Site GB44003
    • London, City Of
      • London, London, City Of, United Kingdom, SW3 6JJ
        • Site GB44101
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Site GB44102
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • University of Arizona
      • Tucson, Arizona, United States, 85724
        • The University of Arizona Medical Center
    • California
      • Bakersfield, California, United States, 93309
        • CBCC Global Research, Inc. at Comprehensive Blood and Cancer
      • Duarte, California, United States, 91010
        • City of Hope Nat'l Medical Center
      • Fullerton, California, United States, 92835
        • St. Jude Hospital Yorba Linda
      • Huntington Beach, California, United States, 92648
        • Pacific Shores Medical Group
      • Loma Linda, California, United States, 92354
        • Loma Linda University
      • Los Angeles, California, United States, 90025
        • The Angeles Clinic and Research Institute
      • Sacramento, California, United States, 95817
        • University of California Davis
      • San Francisco, California, United States, 94143
        • University of California - San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Connecticut
      • Middletown, Connecticut, United States, 07748-3052
        • Memorial Sloan Kettering Cancer Center
    • Florida
      • Hollywood, Florida, United States, 33021
        • Memorial Cancer Institute - West
      • Miami, Florida, United States, 33136
        • University of Miami
      • Orlando, Florida, United States, 32806
        • Orlando Health Inc
      • Pembroke Pines, Florida, United States, 33028
        • Memorial Hospital West
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Cancer Treatment Centers of America, Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • Northwestern University Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40217
        • Norton Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center(UMMC)Transplant Center
      • Brandywine, Maryland, United States, 20613
        • Maryland Oncology Hematology
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114-2696
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Minnesota
      • Saint Louis Park, Minnesota, United States, 55426
        • Health Partners Institute
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Cancer Center
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Cancer Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Cancer Center
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10029-6574
        • Mount Sinai School of Medicine
      • Stony Brook, New York, United States, 11794-9452
        • Stony Brook University Medical Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center
      • Middletown, Ohio, United States, 45042
        • Precision Cancer Research -Dayton Physicians Network
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Science Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
      • Portland, Oregon, United States, 97213
        • Earle A. Chiles Research Institute
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17604
        • Lancaster General Hospital
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19124
        • Cancer Treatment Centers of America, Philadelphia
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital-Lifespan Cancer Institute
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Md Anderson Cancer Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Dwight and Martha Schar Cancer Institute
    • Washington
      • Auburn, Washington, United States, 98801
        • MultiCare Regional Cancer Center - Gig Harbor
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female subject eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin and a demonstrated non-pregnant status through additional testing are eligible) and at least one of the following conditions applies:

    • Not a woman of child-bearing potential (WOCBP) OR
    • WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs
  • 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 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
  • A sexually active male subject with a female partner(s) who is 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.
  • Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 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 has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
  • Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
  • Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
  • Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
  • Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
  • Subject has ECOG performance status 0 to 1.
  • Subject has predicted life expectancy ≥ 12 weeks.

  • Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.

    • Hemoglobin (Hgb) ≥ 9 g/dL. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
    • Absolute neutrophil count (ANC) ≥ 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) without liver metastases (or < 3.0 x ULN if liver metastases are present)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
    • Estimated creatinine clearance ≥ 30 mL/min
    • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)

Exclusion Criteria:

  • Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies, as long as it was completed at least 6 months prior to randomization. Subject may have received treatment with herbal medications that have known antitumor activity > 28 days prior to randomization.
  • Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ 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. Subjects 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 received other investigational agents or devices within 28 days prior to randomization.
  • Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
  • Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
  • Subject has prior severe allergic reaction or intolerance to any component of mFOLFOX6.
  • Subject has known dihydropyrimidine dehydrogenase deficiency.
  • Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
  • Subject has significant gastric bleeding and/or untreated gastric ulcers that would exclude the subject from participation.

  • Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen (HBs Ag)) or 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 (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
    • Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
    • Subjects treated for HCV with undetectable viral load results are eligible.
  • Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
  • Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.

  • Subject has significant cardiovascular disease, including any of the following:

    • Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) 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
    • History or family history of congenital long QT syndrome
    • Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
  • Subject has a history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
  • Subject has known peripheral sensory neuropathy > Grade 1 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 is without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
  • Subject has 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 comorbid 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (zolbetuximab plus mFOLFOX6)
Participants will receive a loading dose of zolbetuximab at Cycle 1 Day 1 followed by a lower dose in subsequent cycles every 3 weeks. Additionally, participants will receive up to 12 treatments of mFOLFOX6 (or components of mFOLFOX6 if some components are discontinued due to toxicity) over 4 or more cycles (each cycle is approximately 42 days) in which mFOLFOX6 is administered on Days 1, 15 and 29. After 12 mFOLFOX6 treatments, participants may continue to receive fluorouracil (5-FU) and folinic acid at the investigator's discretion until the subject meets study treatment discontinuation criteria.
Drug: zolbetuximab
Zolbetuximab will be administered as a minimum 2-hour IV infusion.
Other Names:
  • IMAB362
Drug: oxaliplatin
Oxaliplatin will be administered as a 2-hour IV infusion
Drug: folinic acid
Folinic acid will be administered as a 2-hour IV infusion.
Drug: fluorouracil
Fluorouracil will be administered as IV bolus over 5-15 minutes and continuous IV infusion over 46-48 hours.
Placebo Comparator: Arm B (Placebo plus mFOLFOX6)
Participants will receive placebo starting at Cycle 1 Day 1 and every 3 weeks thereafter. Additionally, participants will receive up to 12 treatments of mFOLFOX6 (or components of mFOLFOX6 if some components are discontinued due to toxicity) over 4 or more cycles (each cycle is approximately 42 days) in which mFOLFOX6 is administered on Days 1, 15 and 29. After 12 mFOLFOX6 treatments, participants may continue to receive fluorouracil (5-FU) and folinic acid at the investigator's discretion until the subject meets study treatment discontinuation criteria.
Drug: oxaliplatin
Oxaliplatin will be administered as a 2-hour IV infusion
Drug: folinic acid
Folinic acid will be administered as a 2-hour IV infusion.
Drug: fluorouracil
Fluorouracil will be administered as IV bolus over 5-15 minutes and continuous IV infusion over 46-48 hours.
Drug: placebo
Placebo will be administered as a minimum 2-hour IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Up to 13 months
PFS is defined as the time from the date of randomization until the date of radiological progressive disease (per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by Independent Review Committee (IRC)) or death from any cause, whichever is earliest.
Up to 13 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 23 months
OS is defined as the time from the date of randomization until the date of death from any cause.
Up to 23 months
Objective Response Rate (ORR)
Time Frame: Up to 13 months
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 Independent Review Committee (IRC) per RECIST 1.1.
Up to 13 months
Duration Of Response (DOR)
Time Frame: Up to 13 months
DOR, defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.
Up to 13 months
Safety and tolerability assessed by adverse events (AEs)
Time Frame: Up to 16 months
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.
Up to 16 months
Number of participants with laboratory assessments abnormalities and or adverse events
Time Frame: Up to 14 months
Number of participants with potentially clinically significant laboratory values.
Up to 14 months
Number of participants with vital signs abnormalities and or adverse events
Time Frame: Up to 14 months
Number of participants with potentially clinically significant vital sign values.
Up to 14 months
Number of participants with electrocardiograms (ECG) abnormalities and or adverse events
Time Frame: Up to 14 months
Number of participants with potentially clinically significant ECG values.
Up to 14 months
Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events
Time Frame: Up to 13 months
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 13 months
Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30) questionnaire
Time Frame: Up to 16 months
The EORTC-QLQ-C30 is a cancer-specific instrument consisting of 5 functional domain scales: physical, role, emotional, social and cognitive.
Up to 16 months
HRQoL measured by the QLQ-OG25 questionnaire
Time Frame: Up to 16 months
The EORTC-QLQ-OG25 instrument evaluates Gastric and GEJ cancer-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion.
Up to 16 months
HRQoL measured by the Global Pain (GP) questionnaire
Time Frame: Up to 16 months
The GP instrument is a single assessment of overall pain.
Up to 16 months
HRQoL measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire
Time Frame: Up to 16 months
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also 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 16 months
Time to confirmed deterioration (TTCD)
Time Frame: Up to 16 months
Calculated using the physical function (PF), OG25-Pain and Global Health Status (GHS)/QoL scores as measured by EORTC QLQ-C30 and QLQ-OG25. TTCD is defined as time to first confirmed deterioration (time from randomization to first clinically meaningful deterioration that is confirmed at the next scheduled visit).
Up to 16 months
PK of zolbetuximab: Concentration Immediately Prior to Dosing at multiple dosing (Ctrough)
Time Frame: Up to 16 months
Ctrough will be derived from the PK serum samples collected.
Up to 16 months
Number of anti-drug antibody (ADA) Positive Participants
Time Frame: Up to 16 months
Immunogenicity will be measured by the number of participants that are ADA positive.
Up to 16 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Astellas Pharma Global Development, Inc.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2018

Primary Completion (Actual)

September 9, 2022

Study Completion (Estimated)

May 31, 2025

Study Registration Dates

First Submitted

April 12, 2018

First Submitted That Met QC Criteria

April 12, 2018

First Posted (Actual)

April 20, 2018

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8951-CL-0301
  • 2017-002567-17 (EudraCT Number)
  • CTR20190258 (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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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