Gastric cancer, esophageal cancer, or gastroesophageal junction adenocarcinoma gastric, gastroesophageal junction, or esophageal adenocarcinoma
Conditions
Interventions
Participants eligible for this study must have HER2-negative, locally advanced or metastatic gastroesophageal adenocarcinoma (GEA) tumors that are CLDN18.2 positive and PD-L1 positive. Participants mu
D013274,D004938
Sponsors
Xu Clair
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ## Inclusion Criteria Subjects must meet all of the following criteria to be eligible for enrollment into the study. 1. Male or female subjects aged >=18 years at the time of first administration of study treatment. Subjects enrolled in South Korea must be aged >=19 years. 2. Subjects with unresectable, locally advanced, or metastatic histologically confirmed gastric cancer (GC), gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma (EAC). 3. Subjects who are treatment naive and have received no prior systemic therapy for advanced or metastatic disease. Note: Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, or chemoradiotherapy is permitted, provided that the last administration of the last regimen (whichever was administered last) occurred at least 6 months prior to randomization. 4. Positive CLDN18.2 expression defined as membrane staining intensity score >=1+ in >=1% of tumor cells using slides prepared from fresh or archival tumor tissue blocks, as assessed either locally using a research-grade immunohistochemistry (IHC) assay or centrally using the Ventana SP455 IHC Assay. Note: Subjects may be enrolled based on CLDN18.2 results obtained from a locally sourced research-grade IHC assay; however, submission of a tumor tissue sample (preferably from the same tumor lesion) for central testing using the Ventana SP455 IHC Assay is required. 5. Positive PD-L1 expression defined as a combined positive score (CPS) >=1 using slides prepared from fresh or archival tumor tissue blocks, as assessed either locally using a research-grade IHC assay or centrally using the PD-L1 IHC 28-8 pharmDx assay (Agilent/Dako). Note: Subjects may be enrolled based on a locally obtained PD-L1 expression result (CPS >=1 or tumor area positivity [TAP] >=1%) using a research-grade IHC assay; however, submission of a tumor tissue sample (preferably from the same tumor lesion) for central testing and confirmation of CPS result using the PD-L1 IHC 28-8 pharmDx assay (Agilent/Dako) is required. 6. At least 1 measurable lesion according to RECIST version 1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Subjects who are willing and able to provide written informed consent and comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 9. Estimated life expectancy of >=90 days. 10. All adverse events (AEs) resulting from prior anticancer therapies have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 Grade =2000/uL * Absolute neutrophil count (ANC) >=1500/uL (>=1.5 x 10^9/L) without growth factor support for 7 days (14 days for pegfilgrastim) prior to screening laboratory assessments or study treatment * Platelet count >=100,000/uL (>=100 x 10^9/L) without transfusion support within 14 days prior to screening laboratory assessments or study treatment * Hemoglobin >=9.0 g/dL without transfusion support within 7 days prior to screening laboratory assessments or study drug administration * Prothrombin time (PT) <=1.5 x upper limit of normal (ULN), or 11 to 15 seconds in the absence of a defined normal range; partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) <=1.5 x ULN; or international normalized ratio (INR) <=1.5 x ULN
Exclusion criteria
Exclusion criteria: ## Exclusion Criteria Subjects who meet at least 1 of the following criteria are not eligible for participation in the study. 1. Subjects with known HER2-positive tumor status. 2. Subjects who experienced a second malignancy within the last 3 years, with the exception of cutaneous squamous cell carcinoma, cutaneous basal cell carcinoma, or cervical carcinoma in situ. 3. Subjects with unstable or active ulcer disease or gastrointestinal bleeding within 6 weeks prior to the first dose of study treatment, unless the investigator determines that the subject is safe to participate. 4. Subjects with active autoimmune disease as determined by any of the following: * Requiring systemic treatment within the past 2 years (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) * Chronic systemic steroid therapy at doses >10 mg prednisone equivalent * Any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or short-term steroid use for hypersensitivity reactions to intravenous (IV) contrast agents is not considered systemic immunosuppressive treatment and is permitted. 5. Subjects with concurrent or prior pneumonitis or interstitial lung disease, regardless of onset timing or requirement for treatment. 6. Subjects currently receiving treatment in another therapeutic clinical trial. 7. Subjects who underwent major surgery or experienced significant traumatic injury within 4 weeks prior to the first dose of study treatment and have not fully recovered, or subjects anticipating or planning major surgery within 6 months after enrollment. 8. Subjects who received chest radiotherapy 50% of pelvic bone volume or equivalent), or limited-field palliative radiotherapy =1000 cps/mL or 200 IU/mL), known hepatitis C infection (hepatitis C antibody [HCVAb] positive and hepatitis C virus [HCV]-RNA positive), uncontrolled human immunodeficiency virus (HIV), HBV, or HCV infection, or diagnosed immunodeficiency. 12. Subjects who received a live vaccine within 30 days prior to the first dose of study treatment or any vaccine within 7 days prior to planned first dose of study treatment. 13. Subjects treated with botanical preparations (e.g., herbal supplements or traditional Chinese medicines)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ## Primary Outcomes 1. To compare progression-free survival (PFS) as assessed by blinded independent central review (BICR) between subjects receiving givastomig in combination with nivolumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) or capecitabine plus oxaliplatin (CAPOX) and subjects receiving control treatment consisting of nivolumab plus mFOLFOX or CAPOX. 2. To evaluate the safety of givastomig in combination with nivolumab plus mFOLFOX or CAPOX. | — |
Secondary
| Measure | Time frame |
|---|---|
| ## Secondary Outcomes 1. To compare objective response rate (ORR), duration of response (DOR), best overall response (BOR) as assessed by blinded independent central review (BICR), and overall survival (OS) between subjects receiving givastomig in combination with nivolumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) or capecitabine plus oxaliplatin (CAPOX) and subjects receiving control treatment consisting of nivolumab plus mFOLFOX or CAPOX. Tumor response will be assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). 2. To assess the relationship between tumor biomarkers, including CLDN18.2 and PD-L1 expression, and efficacy and safety outcomes in subjects receiving givastomig in combination with nivolumab plus mFOLFOX or CAPOX. 3. To compare electronic patient-reported outcomes (ePROs) between treatment groups using the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire for Oesophago-Gastric Cancer (EORTC QLQ-OG25), and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire in subjects receiving givastomig in combination with nivolumab plus mFOLFOX or CAPOX and subjects receiving control treatment consisting of nivolumab plus mFOLFOX or CAPOX. | — |
Countries
China, Japan, United States
Contacts
Public ContactToshio Sugimoto
Clinipace KK
Outcome results
None listed