Adenocarcinoma
Conditions
Brief summary
This study primarily evaluates the efficacy and safety of the LM-302 plus tislelizumab regimen versus tislelizumab plus chemotherapy in the treatment of previously untreated locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma patients with CLDN18.2 positivity.
Interventions
DRUGLM-302 Injection
The LM-302 injection is an ADC drug targeting CLDN18.2.
DRUGTislelizumab
Tislelizumab is a humanized monoclonal antibody targeting programmed cell death receptor-1 (PD-1).
Oxaliplatin injection is a platinum-based antitumor drug.
DRUGCapecitabine Tablets
Capecitabine tablets belong to the fluorouracil-class prodrugs.
Sponsors
Shanghai Chia Tai Tianqing Pharmaceutical Technology Development Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to comply with the study's visit schedule, treatment plan, laboratory tests, and other research procedures. * Age ≥ 18 years. * Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction. * For locally advanced unresectable or metastatic adenocarcinoma of the stomach or gastroesophageal junction that has not previously received any systemic treatment: * Patients who have previously received radical neoadjuvant chemotherapy or adjuvant chemotherapy (radiotherapy) based on a platinum-based combination chemotherapy regimen and have not developed distant metastasis or local recurrence within 6 months after completion of treatment can be included. * The calculation of a 6-month interval is defined as recurrence within the same date range after 6 months. For example, if the end date of the last treatment is January 1, the 6-month period from that date refers to January 1 to July 1 (including July 1). Alternatively, if the end date of the last treatment is August 31, the 6-month period from that date refers to August 31 to February 28 (or February 29 in leap years). * Archived specimens or fresh tumor tissue specimens from ≤3 years ago must be provided for CLDN18.2 and PD-L1 testing (PD-L1 results are not a condition for enrollment). When multiple samples are present, the most recent accessible and qualified sample must be provided. After confirmation by the central laboratory, tumor tissue with positive CLDN18.2 expression is defined as ≥25% tumor cell membrane staining intensity 2+ \& 3+. For patients who have previously received radical neoadjuvant chemotherapy or adjuvant chemotherapy (radiotherapy) based on platinum-containing combination chemotherapy regimens, newly obtained tissue from recurrent or metastatic lesions must be provided for CLDN18.2 and PD-L1 testing. * A negative report on the expression detection of human epidermal growth factor receptor-2 (HER2) in tumor tissue must be provided. The definition of HER2 negative expression is ImmunoHistoChemistry (IHC) score 0/1+, IHC score 2+, and fluorescence in situ hybridization (FISH) negative. * According to the RECIST 1.1 evaluation criteria, there must be at least one measurable lesion. * Expected survival duration ≥ 3 months. * According to the Eastern Cooperative Oncology Group (ECOG) standards, the physical performance status score is 0 or 1. * Good organ function: a. Bone marrow reserve: Platelets (PLT) ≥ 100×10\^9/L, absolute neutrophil count (ANC) ≥ 1.5×10\^9/L, Hemoglobin (Hb) ≥ 90 g/L (no blood transfusion or supportive treatment such as colony-stimulating factors within 14 days prior to hematology parameter examination during the screening period); b. Coagulation function: International normalized ratio (INR) ≤ 1.5, Activated partial thromboplastin time (APTT) ≤ 1.5×upper limit of normal (ULN); c. Liver function: Total bilirubin ≤ 1.5×ULN, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) ≤ 2.5×ULN (if there is liver metastasis, then ALT and AST ≤ 5×ULN) and Albumin (ALB) ≥ 30 g/L; d. Renal function: Creatinine clearance rate ≥ 50 mL/min (calculated according to the Cockcroft-Gault formula); e. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; QT interval (QTcF) ≤ 470 ms for females and ≤ 450 ms for males. * Women of childbearing age must have a negative blood pregnancy test within 7 days before administration; any fertile male and female subjects must agree to use highly effective contraception throughout the study medication period and for 7 months after the last dose of the study. Males must agree to refrain from donating sperm during the study period and for 7 months after the last dose of the study. Females must agree to refrain from breastfeeding during the study period.
Exclusion criteria
* Other pathological types confirmed by histopathology, such as squamous cell carcinoma, sarcoma, or undifferentiated carcinoma. * There are gastric cancer lesions confirmed by imaging that are accompanied by cavities or necrosis, and are closely related to major blood vessels, and are assessed by the researchers as posing a high risk of major bleeding. * Patients with known central nervous system (CNS) metastases. Patients with non-meningeal, midbrain, pontine, or spinal cord metastases who are judged by the investigator to have stable brain metastases can be enrolled. Stable brain metastases are defined as patients whose brain metastases have undergone treatment and the condition of the metastases has stabilized (brain imaging examination at least 28 days before randomization shows stable lesions, no neurological symptoms, and no immediate need for local or systemic treatment within 14 days before randomization), with no evidence of new or previously existing brain metastases enlarging. * Clinically uncontrollable third-space effusion, such as moderate or greater volume, requiring long-term catheterization, previous history of intestinal obstruction or paralysis, compartmented ascites, undergoing or planning to undergo local treatment (including drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy) within 14 days prior to screening, or significant increase within 2 weeks after local treatment, meeting any of the above criteria or deemed unsuitable for enrollment by the investigator. * Patients with symptomatic spinal cord compression, or those who are expected to develop symptoms of spinal cord compression if left untreated; or for patients with previously diagnosed and treated spinal cord compression, there is no evidence indicating that the disease was clinically stable for ≥4 weeks before the first study drug administration; except for patients with asymptomatic spinal cord compression indicated by imaging, who are assessed as stable by a specialist and do not require treatment for spinal cord compression at this time. * Accompanied by severe peritoneal metastasis, the main manifestations are: clinically significant intestinal obstruction; barium enema indicating small intestinal stenosis. * History of gastrointestinal perforation or gastrointestinal fistula within the previous 6 months. If the perforation or fistula has been treated through resection or repair surgery, and the condition is assessed by the investigator as having been cured or controlled, participation in the study is permissible. * Poorly controlled tumor-related pain: * For patients requiring analgesic treatment, a stable dosage of treatment must be established before participating in the study. * Symptomatic lesions suitable for palliative radiotherapy (such as bone metastasis or metastasis causing nerve damage) should be treated before enrollment. * Before enrollment, if appropriate, consideration should be given to local treatment for asymptomatic metastatic lesions that may lead to functional deficits or intractable pain due to further growth (e.g., epidural metastasis not currently associated with spinal cord compression). * Patients with a body weight of less than 35kg or a body weight loss of more than 10% within 2 months prior to signing the informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 1.5 years | To compare the progression-free survival (PFS) of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who were previously untreated and had a PD-L1-positive status (CPS≥1) and high CLDN18.2 expression (≥75% 2+\&3+) with the LM-302 plus tislelizumab regimen versus the tislelizumab plus chemotherapy regimen in the LM-302 plus tislelizumab group and in all randomized populations. The PFS was assessed using blind independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | During the study period (Baseline up to two years) | The preriod from the first use of the drug to death from all causes. For subjects who are still alive at the last follow-up, the OS will be counted as data censored based on the last follow-up. For subjects who are lost follow-up, the OS will be counted as data cesored based on the last confirmed survival time before being lost to follow-up. |
| Progression-free survival (PFS) assessed by Investigator | During the study period (Baseline up to two years) | The period from the first use of the drug to disease progression or death (whichever occurs first). |
| Objective Response Rate (ORR) | During the study period (Baseline up to two years) | The period from firstly-recorded objective tumor response (CR or PR) to firstly-recorded objective tumor progression or death due to any cause (whichever occurs first). |
| Disease Control Rate (DCR) | During the study period (Baseline up to two years) | Proportion of subjects whose tumors shrink or remain stable for a certain period, including complete remission (CR), partial remission (PR) and stable disease (SD). |
| Objective response rates (ORR) | During the study period (Baseline up to two years) | Proportion of patients whose tumors shrank by a certain amount and remained for a certain period of time, including complete response (CR) and partial response (PR) cases. |
| Number of subjtecs with incidence of adverse events | During the study period (Baseline up to two years) | Number of subjtecs with incidence of adverse events: Occurrence of all adverse events (AE), serious adverse events (SAE), and treatment-related adverse events (TEAEs) |
Countries
China
Contacts
CONTACTLin Shen, Doctor
Outcome results
None listed