A Phase 3, Global, Multi-center, Double-blind, Randomized Study of ASP2138 Plus Chemotherapy (CAPOX or mFOLFOX6) With Pembrolizumab vs Placebo Plus Chemotherapy With or Without Pembrolizumab in First-line Treatment of Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma in Participants Whose Tumors Are HER2-negative and Claudin (CLDN) 18.2-positive
Claudin 18.2 or CLDN18.2 is a protein found on cells in the digestive system. It is also found in some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to CLDN18.2 and a type of immune cell called a T cell. This tells the immune system to attack the tumor. ASP2138 is a potential treatment for people with gastric cancer (also known as stomach cancer) or gastroesophageal junction cancer (GEJ cancer). GEJ is where the tube that carries food (esophagus) joins the stomach. This study is for people with gastric or GEJ cancer that has spread nearby (locally advanced) and is not removable by surgery (unresectable), or has spread to other parts of the body (metastatic). It is for those whose cancer is human epidermal growth factor receptor 2 (HER2)-negative and CLDN18.2-positive. HER2-negative means the cancer does not have extra HER2 protein, so medicines that target HER2 do not work and are therefore not used. CLDN18.2-positive means people have a certain amount of CLDN18.2 proteins on their cancer cells. In this study, researchers want to learn if ASP2138 given together with standard treatments (chemotherapy and pembrolizumab) help people with HER2-negative and CLDN18.2-positive gastric or GEJ cancer. The main aim is to learn how long people who are given ASP2138 with chemotherapy and pembrolizumab live without their cancer getting worse, compared with placebo given with chemotherapy with or without pembrolizumab, and if they live for longer. Placebo looks like the study treatment but does not have any medicine in it. The main aim of this study is to check how well ASP2138 works when given together with chemotherapy and pembrolizumab compared with placebo plus chemotherapy with or without pembrolizumab. People aged 18 years or older with locally advanced unresectable or metastatic gastric or GEJ cancer can take part. Their tumor should be HER2-negative and CLDN18.2-positive. The study doctors will check people for any health conditions that can exclude them from taking part, interfere with the study procedures, or pose an unacceptable risk. This is a double-blind study. That means the people and the study doctors will not know who will receive which treatment. People will be assigned to one of 2 treatment groups by chance: Group A: People will receive ASP2138 along with chemotherapy and pembrolizumab. Group B: People will receive placebo along with chemotherapy, with or without pembrolizumab. People will keep receiving treatment until their cancer gets worse, they have medical problems that require stopping treatment, or a study rule says they must stop. There will be regular safety checks. People will continue to have scans of their tumor until their cancer becomes worse.
• Participant has histologically or cytologically confirmed gastric or GEJ adenocarcinoma.
• Participant has radiographically confirmed, locally advanced unresectable or metastatic disease within 28 days prior to randomization.
• Participant has predicted life expectancy \>= 12 weeks.
• Female participant is not pregnant and at least 1 of the following conditions apply:
‣ Not a women of childbearing potential (WOCBP)
⁃ WOCBP who has a negative serum pregnancy test at screening and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention. (Note: For screening, participants with elevated serum human chorionic gonadotropin (HCG) and a demonstrated nonpregnant status through additional testing are eligible.)
• Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period, and at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 6 months after the final administration of study intervention.
• Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after the final administration of study intervention.
• Male participant must not donate sperm during the treatment period and for 6 months after the final administration of study intervention.
• Participant has radiologically evaluable disease (measurable and/or non measurable) according to RECIST V1.1, per investigator assessment, \<= 28 days prior to randomization. For participants 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.
• Participant's tumor is HER2-negative (HER2 immunohistochemistry (IHC) score 0+/1+ or HER2 IHC score 2+/in situ hybridization (ISH) negative) as determined by local or central testing.
• Participant has provided an formalin-fixed paraffin-embedded (FFPE) tumor sample which meets the requirements of the study as specified in the laboratory manual.
• Participant has CLDN18.2-positive tumor as determined by central testing.
• Participant has a valid programmed death-ligand 1 (PD-L1) result as determined by central testing of a tumor sample.
• Participant with known microsatellite instability-high or mismatch repair deficient status may enroll as long as their tumor expresses PD-L1 combined positive score (CPS) \>= 1 as determined by central IHC testing.
• Participant has ECOG performance status 0 to 1.
• Participant must meet all of the criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In case of multiple central laboratory data within this period, the most recent data should be used (transfusion is allowed, but posttransfusion hemoglobin \[24 hours or later following transfusion\] must be \>= 9 g/dL).
∙ South Korea Specific:
• Participant is \>= 19 years of age at the time of signing informed consent.
• Female participant is not pregnant and at least 1 of the following conditions apply:
‣ Not a WOCBP
⁃ WOCBP who has a negative serum pregnancy test at screening and agrees to follow the contraceptive guidance from the time of informed consent through at least 15 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention. (Note: For screening, participants with elevated serum HCG) and a demonstrated nonpregnant status through additional testing are eligible.)
• Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period, and at least 15 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for at least 15 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period, and for 12 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 12 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Male participant must not donate sperm during the treatment period and for 12 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
∙ Japan Specific:
• Female participant is not pregnant and at least 1 of the following conditions apply:
‣ Not a WOCBP
⁃ WOCBP who has a negative serum pregnancy test at screening with a medical interview and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention. (Note: For screening, participants with elevated serum HCG and a demonstrated nonpregnant status through additional testing are eligible.)