AACR Adaptive Biomarker-Driven Organ Preservation Trial in Gastroesophageal Adenocarcinomas
This study is testing a personalized treatment approach for stomach or esophageal cancer (gastroesophageal adenocarcinoma). It uses a combination of chemotherapy (Leucovorin, Oxaliplatin, Fluorouracil), immunotherapy (Tislelizumab), and targeted therapy (Zanidatamab) based on specific markers in your tumor, like HER2, MSI, and PD-L1. You would first have your tumor tested for these markers. If a match is found, you would receive a tailored treatment plan for about four months before surgery, and then for up to eight months after surgery. The main goals are to see how many patients have a complete response to treatment before surgery and how many can avoid surgery or have their organs preserved.
- Study design
- This is a multi-center, open-label study with a planned enrollment of 242 participants. It has two stages, with treatment tailored to your tumor's biomarkers.
- What's involved
- You would undergo tumor biopsies for biomarker analysis and may receive one cycle of standard chemotherapy while awaiting results. If eligible, you would receive treatment for about four months before surgery and up to eight months after surgery.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your organ preservation rate will be measured up to 12 months after treatment.
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NCT07290985
AACR Adaptive Biomarker-Driven Organ Preservation Trial in Gastroesophageal Adenocarcinomas
Recruiting
PHASE2Ages 18+InterventionalTreatmentAmerican Association for Cancer ResearchInvestigator-initiated
~242 participants
Updated 2026-07-23 on ClinicalTrials.gov
What's tested:TislelizumabLeucovorinOxaliplatinFluorouracilZanidatamabZolbetuximab
At a glance
Recruiting sites
3 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Pathological Complete Response (pathCR) Rate (Stage I).
Measured over At time of surgery.
+1 more outcome measured
Conditions
Where it's being run
3 sites across 3 statesCalifornia1
Connecticut1
Ontario1
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Histologically confirmed, resectable adenocarcinoma of the stomach, esophagus, or gastroesophageal junction (Stage II or higher, T2N0 with high-risk features).
Complete surgical resection deemed achievable by multidisciplinary evaluation.
Willingness to undergo tumor biopsies for biomarker analysis (HER2, FGFR2b, PD-L1, MSI) at screening, progression, or pre/post- surgery.
Life expectancy ≥ 24 weeks. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
Adequate organ function:
Hematologic: absolute neutrophil count (ANC) ≥1.5 ×10⁹/L, platelets ≥100 ×10⁹/L, hemoglobin ≥ 8 g/dL
Hepatic: aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤2.5 × ULN, total bilirubin ≤1.5 × upper limit of normal (ULN) (≤2.5 × ULN for Gilbert's)
Renal: creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min/1.73 m²
Willingness for blood samples to be drawn for research purposes.
Baseline dihydropyrimidine dehydrogenase (DPD) testing per local guidelines; dosing of 5-FU adjusted for deficiency.
Use of two effective contraception methods for women of childbearing potential and men during and 4 months after study; pregnant or breastfeeding women excluded.
Must have the ability to understand and the willingness to sign a written informed consent document.
Willingness and able to comply with the protocol for the duration of the study, including attending scheduled visits, examinations, the screening procedure, and having their tumor and blood molecularly characterized.
Histologically confirmed diagnosis of resectable (i.e., radical surgery eligible), HER2-positive (defined as 3+ HER2 expression by IHC or 2+ HER2 expression by immunohistochemistry (IHC) with in situ hybridization (ISH)-positivity per central assessment) adenocarcinoma of the stomach or esophagus, including the gastroesophageal junction.
Formalin-fixed, paraffin-embedded (FFPE) tumor sample tested at a central laboratory confirming HER2-positive status.
Left ventricular ejection fraction (LVEF) ≥50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA).
Exclusion
Unresectable disease, peritoneal dissemination, and/or positive cytology on laparoscopy.
Peripheral neuropathy ≥ Grade 2.
Active infection.
Chronic growth factor support for white blood cells or granulocytes.
Concurrent anti-cancer therapy (exceptions: supportive care medications ≥1 month prior, low molecular weight heparin, prior adjuvant hormonal therapy \>3 years, palliative radiation
Local/systemic therapy for current gastroesophageal diagnosis (except one FLOX/ mFOLFOX6 dose during screening).
Significant medical conditions compromising safety or protocol compliance.
Preexisting cardiac conditions.
Stroke, transient ischemic attack (TIA), or myocardial infarction within 6 months.
Prior FGFR-targeted therapy.
Prior HER2-targeted therapy (except \>5 years prior for breast cancer).
Prior checkpoint inhibitor therapy (anti-PD-1/PD- L1/PD-L2).
Conditions preventing safe surgery/biopsy.
Malabsorption syndrome or inability to swallow oral medication.
Pregnant or nursing women
History of stem cell or organ transplant.
Major surgery within 14 days.
Other malignancy within 3 years (exceptions: basal/squamous cell carcinoma, in situ malignancy, low-risk prostate cancer).
Systemic corticosteroids \>10 mg prednisone/ day or immunosuppressive therapy ≤14 days prior (exceptions: adrenal replacement, topical/ inhaled, short prophylactic courses).
HIV with CD4 \<350, active hepatitis B or C.
Active or relapsing autoimmune disease (exceptions: controlled type I diabetes, hypothyroidism on replacement, controlled celiac disease, mild skin disease, other non- recurrent diseases).
History of hypersensitivity or contraindications to any active substance/active ingredient of any study medication, including chemotherapy components monoclonal antibodies, recombinant proteins, and/or any of the excipients listed in the ingredients of any drug formulation
Poorly controlled seizures
Clinically significant bleeding (CTCAE ≥ Grade 3) from the gastrointestinal (GI) tract within 4 weeks prior to enrollment.
Administered a live vaccine ≤ 4 weeks prior to enrollment
History of interstitial lung disease or non-infectious pneumonitis, or with severe dyspnea at rest or requiring supplementary oxygen therapy.
Treated with another investigational product within 28 days of enrolment.
Total lifetime anthracycline load exceeding 360 mg/m² of doxorubicin or equivalent
QTc Fridericia (QTcF) \>470 ms. Note: For subjects with longer QTcF on initial electrocardiogram (ECG), follow-up ECG may be performed in triplicate to determine eligibility (e.g., after correction of electrolyte abnormalities, or discontinuation of QT-prolonging drugs).
Ongoing Grade 2 or greater diarrhea
What this trial measures
- Pathological Complete Response (pathCR) Rate (Stage I).At time of surgery.
Proportion of patients achieving a pathCR in the surgical specimen after perioperative biomarker-directed systemic therapy.
- Organ Preservation Rate (Stage II)Up to 12 months post-treatment.
Proportion of patients able to avoid surgery and preserve the affected organ due to biomarker-driven treatment response.