Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or CancerPhase 3SpotlightNCT03504397
A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer.
A Phase 3 study testing zolbetuximab, oxaliplatin and folinic acid in people with Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer and Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer, run by Astellas Pharma Global Development, Inc. at 218 sites in 20 countries.
Trial summary
Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer, Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer, Metastatic Gastric Adenocarcinoma or Cancer
- What is being tested?
- zolbetuximab, oxaliplatin and folinic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 565 participants
- Where
- 218 sitesin 20 countries
- Study dates
- 21 Jun 2018to 31 Mar 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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.
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- 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.
Trial locations and contacts
218 sites in 20 countries.
218 sites in 20 countries
United States51 sites
MultiCare Regional Cancer Center - Gig Harbor
Auburn, Washington, 98801
University of Colorado
Aurora, Colorado, 80045
CBCC Global Research, Inc. at Comprehensive Blood and Cancer
Bakersfield, California, 93309
University of Maryland Medical Center(UMMC)Transplant Center
Baltimore, Maryland, 21201
Memorial Sloan Kettering Cancer Center
Basking Ridge, New Jersey, 07920
Massachusetts General Hospital
Boston, Massachusetts, 02114-2696
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Maryland Oncology Hematology
Brandywine, Maryland, 20613
Roswell Park Cancer Institute
Buffalo, New York, 14263
Northwestern University Medical Center
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
The Ohio State University Medical Center
Columbus, Ohio, 43210
Memorial Sloan Kettering Cancer Center
Commack, New York, 11725
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope Nat'l Medical Center
Duarte, California, 91010
Inova Dwight and Martha Schar Cancer Institute
Fairfax, Virginia, 22031
St. Jude Hospital Yorba Linda
Fullerton, California, 92835
Memorial Sloan Kettering Cancer Center
Harrison, New York, 10604
Memorial Cancer Institute - West
Hollywood, Florida, 33021
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Pacific Shores Medical Group
Huntington Beach, California, 92648
Lancaster General Hospital
Lancaster, Pennsylvania, 17604
Loma Linda University
Loma Linda, California, 92354
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Norton Cancer Institute
Louisville, Kentucky, 40217
University of Miami
Miami, Florida, 33136
Memorial Sloan Kettering Cancer Center
Middletown, Connecticut, 07748-3052
Precision Cancer Research -Dayton Physicians Network
Middletown, Ohio, 45042
Memorial Sloan Kettering Cancer Center
Montvale, New Jersey, 07645
Mount Sinai School of Medicine
New York, New York, 10029-6574
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Cancer Treatment Centers of America, Atlanta
Newnan, Georgia, 30265
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, 73104
Orlando Health Inc
Orlando, Florida, 32806
Memorial Hospital West
Pembroke Pines, Florida, 33028
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Cancer Treatment Centers of America, Philadelphia
Philadelphia, Pennsylvania, 19124
University of Arizona
Phoenix, Arizona, 85004
Earle A. Chiles Research Institute
Portland, Oregon, 97213
Oregon Health & Science University
Portland, Oregon, 97239
Rhode Island Hospital-Lifespan Cancer Institute
Providence, Rhode Island, 02903
University of California Davis
Sacramento, California, 95817
Health Partners Institute
Saint Louis Park, Minnesota, 55426
Regions Hospital
Saint Paul, Minnesota, 55101
University of California - San Francisco
San Francisco, California, 94143
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Sanford Cancer Center
Sioux Falls, South Dakota, 57104
Stony Brook University Medical Center
Stony Brook, New York, 11794-9452
The University of Arizona Medical Center
Tucson, Arizona, 85724
Memorial Sloan Kettering Cancer Center
Uniondale, New York, 11553
Italy18 sites
Site IT39013
Ancona, 60126
Site IT39004
Bergamo, 24127
Site IT39009
Cremona, 26100
Site IT39011
Meldola, Forli, 47014
Site IT39006
Milan, 20132
Site IT39008
Milan, 20141
Site IT39021
Modena, 41124
Site IT39020
Monza, Lombardy, 20052
Site IT39016
Padova, 35128
Site IT39012
Parma, 43126
Site IT39018
Perugia, 05100
Site IT39003
Piacenza, 29100
Site IT39019
Pisa, 56126
Site IT39022
Reggio Emilia, 42123
Site IT39015
Roma, 00128
Site IT39026
Terni, 5100
Site IT39024
Turin to, 5-10126
Site IT39023
Vicenza, VI, 36100
Japan15 sites
Site JP81013
Bunkyo-ku, Tokyo
Site JP81006
Chuo-ku, Tokyo
Site JP81005
Fukuoka
Site JP81015
Hidaka, Saitama
Site JP81003
Kashiwa, Chiba
Site JP81010
Kitaadachi-gun, Saitama
Site JP81014
Kobe, Hyōgo
Site JP81008
Koto-ku, Tokyo
Site JP81002
Matsuyama, Ehime
Site JP81009
Nagoya, Aichi-ken
Site JP81004
Osaka
Site JP81011
Osaka
Site JP81007
Sapporo, Hokkaido
Site JP81001
Suita, Osaka
Site JP81012
Sunto-gun, Shizuoka
France13 sites
Site FR33008
Besançon, Franche-Comte, 25033
Site FR33010
Brest, Brittany Region, 29609
Site FR33103
Créteil, 94000
Site FR33009
Dijon, Bourgogne-Franche-Comté, 21079
Site FR33003
Lyon, Rhone, 69008
Site FR33011
Montpellier, Languedoc-Roussillon, 34298
Site FR33005
Nice, Provence-Alpes-Côte d'Azur Region, 06200
Site FR33007
Nice, 06189
Site FR33002
Paris, Paris, 75970
Site FR33006
Poitiers, Vienne, 86021
Site FR33001
Rennes, Brittany Region, 35042
Site FR33101
Saint-Herblain, Pays de la Loire Region, 44805
Site FR33104
Saint-Priest-en-Jarez, 42270
Spain13 sites
Site ES34011
Alcorcón, Madrid, 28925
Site ES34010
Ávila, Castille and León, 05004
Site ES34013
Badalona, Barcelona, 08028
Site ES34005
Barcelona, 08003
Site ES34016
Barcelona, 08025
Site ES34015
Barcelona, 08035
Site ES34019
Burgos, 09006
Site ES34008
Madrid, 28007
Site ES34017
Madrid, 28033
Site ES34004
Madrid, 28034
Site ES34003
Murcia, 30120
Site ES34018
Seville, 41009
Site ES34006
Zaragoza, 50009
Brazil12 sites
Site BR55007
Barretos, São Paulo, 14784-400
Site BR55017
Belo Horizonte, 30130-090
Site BR55010
Brasília, Federal District, 70200-730
Site BR55002
Itajaí, Santa Catarina, 88301-220
Site BR55006
Lajeado, Rio Grande do Sul, 95900000
Site BR55016
Passo Fundo, 99010-260
Site BR55015
Rio de Janeiro, 22793-080
Site BR55018
Santa Catarina, 88501-003
Site BR55003
Santo André, São Paulo, 09060-650
Site BR55005
São José do Rio Preto, São Paulo, 15090-000
Site BR55009
São Paulo, 01509-900
Site BR55004
São Paulo, 08270-070
Germany11 sites
Site DE49012
Berlin, 13125
Site DE49011
Berlin, 13353
Site DE49010
Dresden, Saxony, 01307
Site DE49018
Dresden, 1067
Site DE49021
Halle, Saxony-Anhalt, 06108
Site DE49019
Heilbronn, 74078
Site DE49004
Leipzig, Saxony, 04103
Site DE49015
Magdeburg, Saxony-Anhalt, 39104
Site DE49002
Mainz, Rhineland-Palatinate, 55101
Site DE49007
München, Bavaria, 81925
Site DE49008
Munich, Bavaria, 81377
Belgium10 sites
Site BE32005
Bruges, 8310
Site BE32001
Brussels, Bruxelles-Capitale, Région de, 1200
Site BE32002
Brussels, Liege, 1050
Site BE32004
Brussels, 1000
Site BE32011
Charleroi, 6000
Site BE32007
Edegem, Antwerpen, 2650
Site BE32012
Ghent, Oost-Vlaanderen, 9000
Site BE32010
Haine-Saint-Paul, 7100
Site BE32006
Leuven, Vlaams Brabant, 3000
Site BE32008
Mons, Hainaut, 7000
United Kingdom10 sites
Site GB44003
Aberdeen, Aberdeenshire, AB25 2ZN
Site GB44103
Cambridge, CB2 0QQ
Site GB44009
Coventry, CV2 2DX
Site GB44104
Dundee, DD2 4BF
Site GB44008
Leeds, LS7 9TF
Site GB44101
London, London, City of, SW3 6JJ
Site GB44002
London, NW1 2PG
Site GB44004
London, W1G 6AD
Site GB44001
Manchester, M20 4BX
Site GB44102
Sutton, Surrey, SM2 5PT
South Korea8 sites
Site KR82008
Incheon, 21556
Site KR82002
Seongnam-si, Gyeonggi-do, 13620
Site KR82004
Seoul, Seoul Teugbyeolsi, 06351
Site KR82003
Seoul, 03080
Site KR82005
Seoul, 05505
Site KR82007
Seoul, 152-703
Site KR82006
Seoul, 6591
Site KR82009
Suwon, Gyeonggido [Kyonggi-do], 16247
China7 sites
Site CN86009
Beijing, 100030
Site CN86003
Haerbin, Heilongjiang, 150081
Site CN86004
Hangzhou, Zhejiang, 310003
Site CN86005
Hefei, 230022
Site CN86006
Nanjing, Jiangsu, 210008
Site CN86001
Xiamen
Site CN86008
Zhengzhou, 450000
Mexico7 sites
Site MX52001
Aguascalientes, 20230
Site MX52003
Distrito Federal, 06720
Site MX52009
Jalisco, 45030
Site MX52002
Mexico City, Mexico City, 06760
Site MX52007
Mexico City, Mexico City, 3100
Site MX52008
San Luis de Potosi, 78250
Site MX52010
Veracruz, Ver, Veracruz, 91900
Taiwan7 sites
Site TW88608
Kaohsiung City, 80756
Site TW88604
Kaohsiung City, 833
Site TW88605
Kwei-Shan, Taoyuan, 333
Site TW88603
Taichung, 404
Site TW88607
Tainan, 704
Site TW88606
Taipei, 10002
Site TW88601
Taipei, 112
Colombia6 sites
Site CO57009
Bogotá, DC, 110231
Site CO57005
Cali, Valle del Cauca Department
Site CO57001
Cali
Site CO57006
Medellín, Antioquia, 574
Site CO57002
Medellín, 0574
Site CO57007
Montería, Departamento de Córdoba, 230002
Israel6 sites
Site IL97210
HaDarom, 7030000
Site IL97201
Haifa, 3109601
Site IL97209
Holon, 58100
Site IL97202
Jerusalem, 91031
Site IL97206
Kfar Saba, Central District, 44281
Site IL97203
Tel Aviv, 64239
Australia5 sites
Site AU61008
Adelaide, South Australia, 5011
Site AU61002
Douglas, Queensland, 4814
Site AU61006
East Bentleigh, Victoria, 3165
Site AU61007
Kogarah, 2217
Site AU61011
Tugun, Queensland, 4224
Canada5 sites
Site CA15005
Edmonton, Alberta, T6G 1Z2
Site CA15002
Montreal, Quebec, H3T 1M5
Site CA15008
Montreal, Quebec, H4A 3J1
Site CA15009
Saint John, New Brunswick, E2L 4L4
Site CA15011
Toronto, Ontario, M5G 1X5
Peru5 sites
Site PE51003
Arequipa, 4001
Site PE51005
Lima, 15036
Site PE51006
Lima, 15072
Site PE51001
Lima, L27
Site PE51004
San Isidro, Lima region, L27
Poland5 sites
Site PL48002
Brzozów, Podkarpackie Voivodeship, 36-20
Site PL48004
Lublin, Lubusz Voivodeship, 20-090
Site PL48007
Ostrołęka, Masovian Voivodeship, 07-410
Site PL48009
Warsaw, 02-781
Site PL48005
Wieliszew, Masovian Voivodeship, 05-135
Chile4 sites
Site CL56003
Providencia, Santiago Metropolitan, 7500921
Site CL56008
Providencia, 7520378
Site CL56005
Santiago, 8330032
Site CL56007
Valdivia, 5090000
About this study
Official title: 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
Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor. There is an unmet medical need to treat people with advanced stomach cancer or GEJ cancer. This study will give more information about how well zolbetuximab works when given with chemotherapy in adults with advanced stomach cancer or GEJ cancer. In this study, adults with advanced stomach cancer or GEJ cancer will either be given zolbetuximab with chemotherapy or a placebo with chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it. Zolbetuximab with chemotherapy has already been approved to treat gastric cancer and GEJ cancer in some countries. This study is being done in countries where zolbetuximab has not yet been approved for use. If zolbetuximab becomes approved for use in those countries taking part in this study, the study doctor will switch study treatment in those countries to the licensed zolbetuximab. If this happens, people taking part in those countries will leave this study and receive licensed zolbetuximab.
The main aim of the study is to check if zolbetuximab and chemotherapy can prevent or delay the worsening of people's gastric cancer and GEJ cancer compared to placebo and chemotherapy.
Read more
Adults with advanced stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample of their cancer will also have the Claudin 18.2 protein. They may have been previously treated with certain standard therapies, but have not been treated with chemotherapy for their cancer. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.
The study treatments are either zolbetuximab with chemotherapy, or placebo with chemotherapy. People who take part will receive just 1 of the study treatments by chance. Study treatment will be double-blinded. That means that the people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in cycles. The study treatment is given to people slowly through a tube into a vein. This is called an infusion. People will have 4 infusions in 6-week (42-day) cycles as follows:
- Zolbetuximab or placebo - 2 infusions in a cycle.
- Chemotherapy (called modified FOLFOX6 or mFOLFOX6) - 3 infusions in a cycle. The first infusion is combined with zolbetuximab or placebo on day 1 of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will receive mFOLFOX6 for up to 6 months (4 study treatment cycles). After the 6 months people may receive chemotherapy containing folinic acid and fluorouracil instead of mFOLFOX6. People may receive folinic acid and fluorouracil chemotherapy for more than 6 months, or until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will visit the clinic on certain days during their study treatment. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. Also, people in the study will have health checks. On some visits they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample after their study treatment has finished. People will visit the clinic after they stop their study treatment. People who start treatment with licensed zolbetuximab or mFOLFOX6 outside of this study will not need to visit the clinic. People will be asked about any medical problems and will have a health check. People will visit the clinic at 1 month after they stop their study treatment. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. People will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their study treatment or not.
Read the detailed description
After the marketing approval in Japan on 26 Mar 2024, this study continued as "post marketing clinical study" in Japan. In the rest of the countries which participated in this study, this study continued as clinical study.
- Conditions
- Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer, Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer, Metastatic Gastric Adenocarcinoma or Cancer, Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma
- Being tested
- zolbetuximab, placebo, oxaliplatin, folinic acid, fluorouracil
- Keywords
- HER2, IMAB362, leucovorin, fluorouracil, Gastric cancer, claudiximab, zolbetuximab, oxaliplatin, adenocarcinoma, Gastro-Esophageal Junction cancer, HER2 Negative mFOLFOX6
- Medical subject headings
- Adenocarcinoma, Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zolbetuximabDrug
Also called IMAB362
Participants received an IV infusion (as a minimum of 2-hour infusion) of zolbetuximab at a loading dose of 800 mg/m^2 on C1D1 followed by subsequent doses of 600 mg/m^2 every 3 weeks starting from C1D22 until participant meets study treatment discontinuation criteria. Each cycle was approximately 42 days.
placeboDrug
Participants received an IV infusion (as a minimum of 2-hour infusion) of placebo matched to zolbetuximab on C1D1 followed by subsequent doses every 3 weeks starting from C1D22 until participant met study treatment discontinuation criteria. Each cycle was approximately 42 days.
oxaliplatinDrug
Participants received up to 12 treatments of oxaliplatin administered 85 mg/m^2 IV infusion over 2 hours) on Days 1, 15 and 29 of each cycle.. A maximum of 12 doses of oxaliplatin was permitted. Each cycle was approximately 42 days.
folinic acidDrug
Participants received up to 12 treatments of folinic acid administered 400 mg/m^2 IV infusion over 2 hours 4 or more cycles on Days 1, 15 and 29 of each cycle. participants could continue to receive folinic acid on Days 1, 15 and 29 of each cycle at the investigator's discretion or until the participant met the study treatment discontinuation criteria. Each cycle was approximately 42 days.
fluorouracilDrug
Participants received up to 12 treatments of 5-fluorouracil over 4 or more cycles administered by IV bolus 400 mg/m^2 over 5 to 15 minutes followed by 2400mg/m^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Participants could continue to receive 5-fluorouracil on Days 1, 15 and 29 of each cycle at the investigator's discretion or until the participant met the study treatment discontinuation criteria. Each cycle was approximately 42 days.
| Study group | Role | What they receive |
|---|---|---|
| mFOLFOX6 + Zolbetuximab | Experimental | Participants received intravenous (IV) infusion (minimum 2-hour) of zolbetuximab at a loading dose of 800 milligrams per square meter (mg/m^2) on cycle1 day1(C1D1) followed by 600 mg/m^2 every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received upto 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4/more cycles. mFOLFOX6 was administered on Days 1, 15 \& 29 of each cycle (5-FU:400mg/m^2 IV bolus over 5-15 minutes followed by 2400mg/m^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400mg/m^2 IV infusion over 2 hours; oxaliplatin: 85mg/m^2 IV infusion over 2 hours) A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants continued to receive 5-FU \& Folinic acid on Days 1, 15 \& 29 of each cycle at the investigator discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. Receives: Drug: zolbetuximab; Drug: oxaliplatin; Drug: folinic acid; Drug: fluorouracil |
| Placebo plus mFOLFOX6 | Placebo comparator | Participants received an IV infusion (minimum 2-hour infusion) of placebo matched to zolbetuximab on C1D1, followed by subsequent doses every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received up to 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4 or more cycles. mFOLFOX6 was administered on Days 1, 15, and 29 of each cycle (5-fluorouracil: 400 mg/m^2 IV bolus over 5-15 minutes followed by 2400mg/m^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400 mg/m^2 IV infusion over 2 hours; oxaliplatin: 85 mg/m^2 IV infusion over 2 hours). A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants could continue to receive 5-FU and folinic acid on Days 1, 15, and 29 of each cycle at the investigator's discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. Receives: Drug: placebo; Drug: oxaliplatin; Drug: folinic acid; Drug: fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS was 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 independent review committee [IRC]) or death from any cause, whichever was earliest. PD was defined as development of new, or progression of existing metastases to the primary cancer under the study. Kaplan -Meier (KM) estimates was used.
Measured: From date of randomization until the date of first documented radiological progression or date of death from any cause, whichever occurred first (up to 62 months and 18 days)
Secondary outcomes (14)
Overall Survival (OS)
OS was defined as the time from the date of randomization until the date of death from any cause. Kaplan-Meier estimates was used.
Measured: From the date of randomization until 62 months and 18 days
Time to Confirmed Deterioration (TTCD) Using Physical Functioning (PF) as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30)
TTCD: time from randomization to first clinically meaning full deterioration (CMD) that was confirmed at next scheduled visit. EORTC-QLQ-C30 was a 30-item cancer-specific instrument consisting of 5 functional scales (physical,role,emotional,social \& cognitive), 9 symptom scales (fatigue, nausea/vomiting,general pain,dyspnea,insomnia,appetite loss,constipation,diarrhea,financial difficulties) \& global health status scale. Most items were scored 1(not at all) to 4(very much) except for items contributing to global health status/QoL, which were scored 1(very poor) to 7(excellent). All raw domain scores were linearly transformed to 0-100scale with higher scores on symptoms indicate worse health state. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of -13. This was derived from an Exit Survey conducted using Patient Global Impression of Severity/Change(PGIS/PGIC) questionnaires as an anchor for estimating meaningful change. KM estimates was used.
Measured: From the date of randomization until 62 months and 18 days
Time to Confirmed Deterioration (TTCD) Using Oesophago-gastric Questionnaire (OG25) on Abdominal Pain and Discomfort as Measured by EORTC QLQ-OG25
TTCD: time from randomization to first CMD that was confirmed at next scheduled visit. EORTC QLQ-OG25 evaluated gastric and GEJ cancer specific symptoms. A 25 item instrument with 6 scales: dysphagia (3 items), eating restrictions (4 ), reflux (2), odynophagia (2), pain and discomfort (2), anxiety (2), as well as 10 single items: eating in front of others, dry mouth, trouble with taste, body image, trouble swallowing saliva, choked when swallowing, trouble with coughing, trouble talking, weight and hair loss. Items were scored:1: not at all; 2: a little, 3: quite a bit, 4: very much, and were transformed linearly into scores (0 to 100) with higher scores indicating worse symptoms. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of 16.67. This was derived from an Exit Survey conducted to use PGIS/PGIC questionnaires as an anchor for estimating the meaningful change. KM estimates was used.
Measured: From the date of randomization until 62 months and 18 days
Time to Confirmed Deterioration (TTCD) Using Global Health Status as Measured by EORTC QLQ-C30
TTCD: time from randomization to first CMD that was confirmed at the next scheduled visit. The EORTC-QLQ-C30 was 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. Most items were scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which were scored 1 ("very poor") to 7 ("excellent"). All raw domain scores were linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of -10. This was derived from an Exit Survey conducted to use PGIS/PGIC questionnaires as an anchor for estimating the meaningful change. KM estimates was used.
Measured: From the date of randomization until 62 months and 18 days
Objective Response Rate (ORR)
ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as was assessed by IRC per RECIST 1.1. CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.
Measured: From the date of randomization until 62 months and 18 days
Duration Of Response (DOR)
DOR was defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.PD was defined as development of new, or progression of existing metastases to the primary cancer under the sudy.
Measured: From date of first response (CR/PR) until 62 months and 18 day
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An Adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not have to have a causal relationship with this treatment. 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, whether or notconsidered related to the medicinal product. TEAE defined as an AE observed after starting administration of the study drug through 30 days after the last dose.
Measured: From first dose until 62 months and 18 days
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
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.
Measured: Baseline, cycle (C) 1 day (D) 22, D1 and D22 of C2 through C39
Change From Baseline in Health Related Quality of Life (HRQoL) Measured by the EORTC-QLQ-C30 Questionnaire
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. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state.
Measured: Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
Change From Baseline in HRQoL Measured by the QLQ-OG25 Questionnaire
The EORTC-QLQ-OG25 consists of a 25-item instrument that evaluates gastric and GEJ cancer-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion. This module consists of 6 scales: dysphagia (3 items), eating restrictions (4 items), reflux (2 items), odynophagia (2 items), pain and discomfort (2 items) and anxiety (2 items), as well as 10 single items: eating in front of others, dry mouth, trouble with taste, body image, trouble swallowing saliva, choked when swallowing, trouble with coughing, trouble talking, weight loss and hair loss. All questions have four response alternatives (1:not at all; 2:a little, 3:quite a bit, 4:very much). Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 For symptom scales/items, higher scores indicate worse symptoms.
Measured: Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
Change From Baseline in HRQoL Measured by Global Pain (GP)
The GP instrument is a single assessment of overall pain. Participants were assessed in global pain according to the following response categories: 1= no pain (anymore), 2 = less pain, 3 = no change and 4 = more pain.
Measured: Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
Change From Baseline in HRQoL Measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) Questionnaire
EQ-5D-5L is a standardized instrument for use as a measure of health outcomes 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.It was developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. 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.
Measured: Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
Pharmacokinetics (PK) of Zolbetuximab in Serum: Trough Concentration (Ctrough)
Ctrough was defined as the predose concentration at the end of dosing interval.
Measured: Predose on C1D22, C3D1, C5D1, C7D1, C9D1
Number of Participants With Anti-drug Antibodies (ADA)
Immunogenicity will be measured by the number of participants that are ADA positive.
Measured: Predose on C1D1, C1D22, C3D1, C5D1, C7D1, C9D1, 30-day follow up, 90-day follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2018
- Study start21 Jun 2018
- Primary completion9 Sep 2022
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or CancerStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 565 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Medical Lead, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03504397
- Sponsor's protocol ID
- 8951-CL-0301
- Other IDs
- 2017-002567-17, CTR20190258, jRCT2080224032, 2024-511365-11-00, 2017
- Acronym
- Spotlight
- Status last verified
- Sep 2026
- First submitted
- 12 Apr 2018
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
- Expanded access
- Available
Publications
Yamaguchi K, Shoji H, Yasui H, Oki E, Sakai D, Hamaguchi T, Tsuji A, Oshima T, Tsuda M, Minashi K, Yang J, Guerrero A, Ueno Y, Matsangou M, Gourgioti G, Nakanishi Y, Furuki S, Kuwamoto K, Yamada S, Shitara K. Zolbetuximab plus chemotherapy in Japanese patients with claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma: a combined subgroup analysis of the phase 3 SPOTLIGHT and GLOW trials. Gastric Cancer. 2026 Jul;29(4):777-787. doi: 10.1007/s10120-026-01738-7. Epub 2026 May 7.
PubMed 42095986Stratton SP, Pang L, Pugh J, Kouzova M, Baldwin D, McDonald J, Lawrence-Glaze R, Moran S, Guerrero A, Moran D. Analytical and Clinical Performance of the VENTANA CLDN18 (43-14A) RxDx Assay in Gastric and Gastroesophageal Junction Adenocarcinoma Tissue Samples in SPOTLIGHT and GLOW. Mod Pathol. 2025 Dec;38(12):100844. doi: 10.1016/j.modpat.2025.100844. Epub 2025 Jul 16.
PubMed 40680855Shitara K, Shah MA, Lordick F, Bang YJ, Ilson D, Van Cutsem E, Enzinger P, Kim SS, Klempner SJ, Moran D, Park JW, Bhattacharya P, Ajani JA, Xu RH. Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary. Future Oncol. 2024;20(26):1861-1877. doi: 10.1080/14796694.2024.2342107. Epub 2024 May 24.
PubMed 38861294Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023 May 20;401(10389):1655-1668. doi: 10.1016/S0140-6736(23)00620-7. Epub 2023 Apr 15.
PubMed 37068504