Gastric/Gastroesophageal Junction Adenocarcinoma
Conditions
Brief summary
HER2 overexpression is observed in approximately 20% of gastric cancers and gastroesophageal junction (GEJ) cancers, making it a validated target for anti-tumor therapy . In advanced-stage systemic therapy, trastuzumab combined with chemotherapy has demonstrated clinical benefits for HER2-positive gastric and GEJ cancers . However, the combination of trastuzumab and pertuzumab plus chemotherapy did not significantly improve overall survival (OS) compared to trastuzumab monotherapy in HER2-expressed gastric/GEJ cancers . In neoadjuvant therapy for early-stage or locally advanced gastric cancer, there is currently no standardized perioperative regimen for HER2-positive gastric or GEJ cancers, and effective treatment remains challenging . Zanidatamab, a humanized bispecific IgG1-like antibody targeting HER2's ECD4 and ECD2 epitopes, exhibits unique enhanced functionality . Phase II studies (NCT03929666) showed that zanidatamab combined with chemotherapy as first-line therapy for HER2-positive advanced gastroesophageal adenocarcinoma (GEA) demonstrated superior survival benefits and durable responses compared to standard therapy (trastuzumab plus chemotherapy) . A Phase III study (HERIZON-GEA-01, NCT05152147) is now underway to further validate its efficacy when combined with chemotherapy ± tislelizumab versus trastuzumab-based chemotherapy . For previously untreated stage II/III locally advanced gastroesophageal junction adenocarcinoma (cT1-2N+M0, cT3-4aNanyM0) with confirmed HER2 high expression (HER2 3+/2+ FISH+), neoadjuvant zanidatamab combined with chemotherapy (FLOT/SOX/CAPOX) is being explored to evaluate safety and efficacy, potentially offering a new treatment option for HER2-positive GEJ cancers in perioperative settings .
Interventions
Zanidatamab Combined with Chemotherapy as Neoadjuvant Therapy
Sponsors
Xijing 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. Signed informed consent. 2. Histologically/radiologically confirmed Stage II/III (cT1-2N+M0 or cT3-4aNanyM0) Siewert II/III GEJ/gastric adenocarcinoma. 3. HER2-high (IHC 3+/2+FISH+); HER2 2+ requires FISH (no time restriction). 4. Age 18-75, any gender. 5. ECOG 0-1, surgically eligible. 6. Adequate organ function for abdominal surgery. 7. Life expectancy ≥3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major pathological response rate (MPR) | 24 months | MPR is defined as 10% or fewer viable cancer cells from the resected tumor following neoadjuvant treatment |
Secondary
| Measure | Time frame |
|---|---|
| Pathological complete response rate(pCR) | 24 months |
| R0 Resection | 24 months |
| Recurrence Free Survival (RFS) | 5 years |
| Treatment-Emergent Adverse Events | 24 months |
Contacts
Primary ContactXiaohua Li
Backup ContactPengfei Yu
Outcome results
None listed