Gastric Cancer
Conditions
Keywords
Gastric Cancer, IBI 343, Sintilimab
Brief summary
This is a Single-arm, Open-label, Phase 1b/2 Study of IBI343 Combined with Sintilimab Plus Chemotherapy in Previously Untreated, Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Detailed description
This trial is a phase Ib/II study to evaluate the safety, tolerability and efficacy of IBI343 in combination with sintilimab and chemotherapy in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. In dose-escalation stage, patients with CLDN 18.2-positive, HER2-negative were treated with IBI 343, sintilimab, and chemotherapy (oxaliplatin, S-1) as first-line therapy, which followed a 3+3 design. The dose expansion stage aimed to further investigate the safety and preliminary efficacy of recommended phase II dose (RP2D), including Cohort 1 and Cohort 2. In Cohort 1, 25 patients with CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma will be enrolled. In Cohort 2, 15 patients with CLDN18.2-positive, HER2-negative gastric signet-ring cell carcinoma will be enrolled.
Interventions
DRUGIBI343
Subjects in the phase 1b stage will receive IBI343 3/4.5/6mg/kg intravenous infusion (IV) D1 Q3W in 3-week cycles. Subjects in the phase 2 stage will receive IBI343 RP2D intravenous IV D1 Q3W in 3-week cycles.
DRUGSintilimab
Subjects will receive sintilimab 200mg IV D1 Q3W in 3-week cycles.
DRUGOxaliplatin
Subjects will receive oxaliplatin 130mg/m2 IV D1 Q3W in 3-week cycles.
DRUGS-1
Subjects will receive S-1 40-60mg BID PO D1-14 Q3W in 3-week cycles.
Sponsors
Shanghai Jiao Tong University School of Medicine
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Able and willing to sign a written Informed Consent Form (ICF) and to comply with protocol-specified visits and related procedures. 2\. Age was 18-75 years at the time of signing the ICF, and gender was unlimited. 3\. Has histopathologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the gastric/gastroesophageal junction (G/GEJ AC). 4\. No received systemic therapy. 5. Has histopathologically confirmed CLDN18.2-positive disease. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Exclusion criteria
* 1\. Has HER2-positive (defined as immunohistochemistry \[IHC\] 3+, or IHC 2+ and positive by in situ hybridization) disease. 2\. Is currently participating in another interventional clinical study, except when the subject is during survival follow-up of an interventional clinical study. 3\. Has a history of treatment with topoisomerase inhibitor-based antibody-drug conjugate(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | up to 2 years | ORR is defined as the proportion of subjects in the analysis population who achieve confirmed objective response (CR or PR) as assessed by the IRRC per RECIST v1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | up to 2 years | Overall survival (OS) is defined as the time from enrollment to death from any cause. |
| Progression-free survival (PFS) | up to 2 years | Progression-free survival (PFS) is defined as the time from enrollemnt to disease progression or death from any cause. |
| Disease control rate (DCR) | up to 2 years | DCR is defined as the proportion of subjects in the analysis population who achieve disease control (CR, PR, or SD) as determined by the IRRC per RECIST v1.1 criteria. |
| Treatment-related adverse event (TRAE) | up to 2 years | Safety evaluation, such as hematotoxicity, hepatotoxicity, and renal function lab test, done continuously during treatment and the level of serum creatinine will be evaluated by using CTCAE 5.0 during study. |
Countries
China
Contacts
Primary ContactRuijin Hospital, Shanghai Jiao Tong University School of Medic
Outcome results
None listed