Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Conditions
Interventions
Group C (Part C):SHR2554+SHR-1701
Group A (Part A):SHR2554+SHR-A1811 +/- SHR-1316/SHR-1701
Group D (Part D):SHR2554
Group B (Part B):SHR2554+SHR-A1904 +/- SHR-1316/SHR-1701
Sponsors
Harbin Medical University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18-75 years (inclusive) at the time of signing the informed consent; no gender restriction; 2. Requirements for tumor diagnosis and prior antitumor treatments vary according to different study parts and cohorts: (1) For enrollment in Part A cohort: histologically confirmed locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, with documented disease progression or intolerance confirmed by the investigator or medical history after prior treatment with trastuzumab-containing regimens or approved trastuzumab biosimilar regimens; (2) For enrollment in Part B cohort: histologically confirmed locally advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma; either treatment-naive or after prior adequate standard therapy (including fluoropyrimidine- and/or platinum-containing regimens) with documented disease progression or intolerance confirmed by the investigator or medical history; (3) For enrollment in Part C and Part D cohorts: histologically confirmed locally advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma; after prior adequate standard therapy (including fluoropyrimidine- and/or platinum-containing regimens) with documented disease progression or intolerance confirmed by the investigator or medical history; (4) For neoadjuvant/adjuvant therapy, if disease progression occurs during treatment or within 6 months after stopping treatment, it should be considered as first-line treatment failure; 3. For different study cohorts, the biomarker requirements are as follows: (1) Subjects enrolled in Part A must have tumors with high HER2 expression, defined as IHC3 or IHC2 with ISH+; (2) Subjects enrolled in Part B must have tumors positive for Claudin 18.2; Claudin 18.2 positivity is defined as >=1% of tumor cells in the tumor tissue expressing Claudin 18.2 >=1; (3) Subjects enrolled in Part C and Part B must have tumors with HER2 medium/low/negative expression, defined as IHC2 with ISH-, IHC1, or 0; 4. According to RECIST v1.1, there must be at least one measurable tumor lesion (brain metastases or lesions in hollow organs such as the esophagus and stomach cannot be counted as measurable); for subjects with only one measurable lesion who have previously received radiotherapy, the lesion must be outside the prior radiotherapy field or show documented progression post-radiotherapy; 5. Subjects must provide formalin-fixed, paraffin-embedded tumor tissue blocks or unstained tumor specimens (see the Laboratory Manual for details) for enrollment or retrospective testing of HER-2, Claudin 18.2, or PD-L1 expression levels; 6. ECOG performance status of 0 or 1; 7. Expected survival >=12 weeks; 8. Baseline assessment of vital organ function meets the following criteria (no use of any blood components or growth factors for corrective treatment within 14 days prior to screening visit inspections): (1) Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (1,500/mm^3); (2) Hemoglobin (Hgb) >= 9.0 g/dL (90 g/L); (3) Platelet count (PLT) >= 100 × 10^9/L (100,000/mm^3); (4) Albumin >= 3.0 g/dL; (5) Serum total bilirubin = 50 mL/min (calculated using the stan
Exclusion criteria
Exclusion criteria: 1. Presence of difficulty swallowing or other factors affecting the oral use of SHR2554; 2. Presence of untreated or active central nervous system (CNS) tumor metastases, history of leptomeningeal metastases, or current leptomeningeal metastases, or: (1) If CNS metastases are limited to the supratentorial and/or cerebellar regions (i.e., no metastases in the midbrain, pons, medulla, or spinal cord) and have received adequate local treatment (surgery or radiotherapy), with no progression observed in imaging examinations from the completion of local treatment to enrollment, and the participant's neurological symptoms have been stable for at least 2 weeks prior to the first dose without the need for steroid therapy, they can participate in the study (except for the prostate cancer cohort); (2) For asymptomatic participants with a single CNS metastasis, if the metastasis is limited to the supratentorial and/or cerebellar regions (i.e., no metastases in the midbrain, pons, medulla, or spinal cord), no corticosteroid treatment is needed, and the brain metastasis lesion diameter is =1 week prior to the first dose can be enrolled; 5. Presence of poorly controlled tumor-related pain; (1) Participants requiring analgesics can be enrolled if they have a stable analgesic regimen prior to the first dose; (2) Participants with clinically symptomatic lesions suitable for palliative radiotherapy (e.g., bone pain from bone metastases or metastases invading nerves) can be enrolled if treatment is completed and stable for at least 14 days prior to the first dose; (3) For metastatic lesions without clinical symptoms, if further progression may cause functional impairment or refractory pain (e.g., epidural metastases without showing spinal cord compression), participants can be enrolled if such treatment is completed prior to the first dose; 6. Has received any of the following treatments:Plans to receive any other antitumor therapy during this trial; (1) Previously received treatment with compounds of the same mechanism (EZH2 inhibitors); (2) Received other investigational drugs or therapies within 4 weeks prior to the first dose in this study; received chemotherapy, radiotherapy, biological therapy, targeted therapy, or immunotherapy within 4 weeks prior to the first dose in this study (nitrosoureas or mitomycin C within 6 weeks prior to the first dose; oral fluoropyrimidines and small molecule targeted agents within 2 weeks prior to the first dose); palliative radiotherapy or local therapy within 2 weeks prior to the first dose; antitumor traditional Chinese medicine within 1 week prior to the first dose; (3) Underwent any major surgery other than diagnostic or biopsy procedures within 28 days prior to the first
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events (AEs)/serious adverse events (SAEs);Objective Response Rate (ORR) Assessed per RECIST v1.1;Dose-Limiting Toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response;Disease Control Rate (DCR);Progression-Free Survival (PFS);Overall Survival (OS);The blood drug concentration of SHR2554;ADC and toxin concentrations of SHR-A1811 and SHR-A1904;ADA positivity rate and percentage of SHR-A1811 and SHR-A1904; | — |
Countries
China
Contacts
Public ContactYanqiao Zhang
Harbin Medical University Cancer Hospital
Outcome results
None listed