Gastric Adenocarcinoma
Conditions
Brief summary
This study is a multicenter, randomized, open-label, controlled Phase III clinical trial aimed at evaluating the efficacy and safety of JS107 combined with toripalimab XELOX versus sintilimab combined with XELOX as first-line treatment for patients with advanced G/GEJ adenocarcinoma. The research subjects were patients with unresectable locally advanced, recurrent or metastatic G/GEJ adenocarcinoma who were CLDN18.2-positive and HER2-negative and had not received systemic treatment before (except for neoadjuvant/adjuvant therapy that occurred more than 6 months after disease progression/recurrence from the last treatment). The study took BICR-PFS and OS as Dual primary endpoints.
Interventions
DRUGInjection JS107&Toripalimab& Oxaliplatin Injection& Capecitabine
JS107: 2 mg/kg on day 1 Q3W; Toripalimab (T): 240 mg on day 1 Q3W. Capecitabine (C): 750 mg/m² BID Day1-Day14, Q3W，Oxaliplatin 100mg/m² on Day1 Q3W, Maximum of 6 cycles.
DRUGSintilimab& Oxaliplatin Injection& Capecitabine
Sintilimab: 3 mg/kg or 200 mg Day1 Q3W, Capecitabine: 1000 mg/m² BID Day1-Day14, Q3W，Oxaliplatin 130mg/m² on Day1 Q3W, Maximum of 6 cycles.
Sponsors
NingBo Junyan Hongshi Biosciences 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
1. The patient voluntarily participated, provided informed consent, signed a written informed consent form, and had good compliance. 2. Age ≥18 years (including), male and female. 3)Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4）Expected survival period ≥3 months. 5）Patients with HER2-negative, unresectable locally advanced, recurrent, or Metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma confirmed by histology/cytology. 6）Previously untreated for systemic therapy for locally advanced, recurrent, or Metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. 7）Positive for CLDN18.2 by IHC testing at the central laboratory. 8）According to the RECIST v1.1 criteria, the patient has ≥1 measurable lesion. 9）The functional level of the organ meets the requirements of the protocol. 10）Agree to use contraception during the study period; females of reproductive potential will undergo a blood pregnancy test within 7 days prior to randomization, with a negative result.
Exclusion criteria
1. Previously received any drug or cell therapy targeting CLDN18.2 2. Received major surgery, live vaccine administration, or Drug therapy with other investigational medicinal products, or received radiotherapy within 2 weeks prior to randomization. 3. Imaging shows cerebral tumor lesions (unless whole-brain radiotherapy or surgery, etc., local treatment has been completed, and imaging and clinical stability have been assessed according to the protocol) 4)Peripheral neuropathy ≥ Grade 2 5）Idiopathic pulmonary fibrosis, Organising pneumonia, drug-induced pneumonia, idiopathic pneumonia, or evidence of active pneumonia on screening chest computerised tomography (CT) scan 6）Pericardial effusion, Pleural effusion, or ascites with a large volume, or with clinical symptoms, or requiring symptomatic treatment. 7）There is a need for systemic antimicrobial or antiviral therapy for active infection. 8）Subjects who cannot take oral medications, require enteral nutrition to maintain feeding, or have Malabsorption syndrome or other conditions affecting gastrointestinal Malabsorption. 9）Presence of biliary or gastrointestinal obstruction, or persistent recurrent vomiting 10）Weight loss of \>10% within the previous 2 months or severe Malnutrition, known prior to randomization. 11）History of gastrointestinal perforation and/or fistula within the prior 6 months; presence of high-risk Haemorrhage of digestive tract disease or risk of rupture bleeding or gastrointestinal/respiratory fistula 12）Serious cardiovascular and cerebrovascular diseases 13）History of systemic treatment for autoimmune diseases within the past 2 years 14）Randomly selected patients with any other Neoplasm malignant within the past 5 years. 15）Known severe allergic reaction to any ingredient in the study drug formulation 16）Known active Hepatitis B, active Hepatitis C, human immunodeficiency (HIV) infection, or have undergone allogeneic stem cell or Solid organ transplant. 17）Diseases determined by researchers to be unsuitable for participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BICR-PFS | up to 2 years | Progression-Free Survival (BICR-PFS) evaluated based on Blinded Independent Central Review (BICR) (according to the RECIST v1.1 criteria) |
| Overall Survival | up to 5 years | The primary endpoint of overall survival (OS) in this multicenter, randomized, open-label Phase III study is the time from randomization to death from any cause, aiming to compare the benefit between JS107 and investigator's choice of therapy in patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma who have received at least one prior line of systemic therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| INV-PFS | up to 2 years | Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria) |
| BICR-ORR or INV-ORR | up to 2 years | ORR evaluated by investigators or BICR (according to the RECIST v1.1 criteria) |
| BICR-DCR or INV -DCR | up to 2 years | Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria) |
| BICR-DoR or INV -DoR | up to 2 years | DoR (based on the RECIST v1.1 criteria) evaluated by investigators or BICR |
| The incidence rate and severity of AE | up to 2 years | The incidence and severity of adverse events (AEs) evaluated according to the NCI-CTC AE v5.0 standard |
| Valley concentration of JS107 | up to 2 years | Valley concentration of JS107 (including ADC, total antibody, and toxin) |
| Anti-drug antibodies (ADA) for JS107 | up to 2 years | Incidence and titer of anti-drug antibodies (ADA) for JS107 (including ADC, total antibody, and toxin) |
| Incidence of neutralizing antibodies (NAb) to JS107 | up to 2 years | Incidence of neutralizing antibodies (NAb) to JS107 (including ADC, total antibody, and toxin) |
| Blood trough concentration of toripalimab | up to 2 years | To evaluate the blood trough concentration of toripalimab |
| Immunogenicity of toripalimab | up to 2 years | Incidence and titer of anti-drug antibody (ADA) of toripalimab, |
| Incidence of neutralizing antibodies (NAb) to Toripalimab | up to 2 years | ADA-positive samples for the presence of Neutralising antibodies (Nab). |
Countries
China
Contacts
CONTACTBifeng Liu
CONTACTJunliang Li
Outcome results
None listed