Using tumor organoids to guide anti‑HER2 ADC treatment for advanced or metastatic bladder cancer

Study Protocol for Evaluating the Efficacy of Anti-HER-2 Antibody-Drug Conjugates (ADC) in Locally Advanced or Metastatic Bladder Cancer Based on Organoid Technology.

This trial will see if using lab‑grown tumor organoids to pick anti‑HER2 antibody–drug conjugate treatment helps people with locally advanced or metastatic bladder cancer who progressed after platinum chemotherapy live longer.

Quick facts

• Study type: Observational
• Enrollment: 224 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Qilu Hospital of Shandong University (other)
• Drugs / interventions: enfortumab, chemotherapy, trastuzumab, Disitamab
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT07379268 on ClinicalTrials.gov

What this trial studies

This observational controlled trial compares outcomes for patients whose anti‑HER2 ADC treatment is chosen based on tumor organoid drug‑sensitivity testing versus those whose treatment is chosen based on HER2 protein expression by IHC. Eligible patients provide a tumor biopsy that is used to generate organoids and test sensitivity to anti‑HER2 ADCs, and treatment decisions are made accordingly or per IHC results. The primary comparisons are one‑year, two‑year, and three‑year overall survival, analyzed with univariate Kaplan–Meier methods. The study enrolls patients with unresectable locally advanced or metastatic bladder cancer who have progressed after platinum‑based chemotherapy and have ECOG performance status 0–2.

Who should consider this trial

Good fit: Adults 18–80 years with unresectable locally advanced (cT4b and/or N2–3) or metastatic (M1) bladder cancer who progressed after at least one platinum chemotherapy regimen, have ECOG 0–2, and can tolerate ADC treatment are ideal candidates.

Not a fit: Patients whose tumors cannot be grown as organoids, who have poor performance status or major comorbidities, or whose tumors lack actionable HER2 biology may not benefit from organoid‑guided anti‑HER2 ADC selection.

Why it matters

Potential benefit: If successful, this approach could better match patients to anti‑HER2 ADCs, increasing the chance of benefit and avoiding ineffective therapies.

How similar studies have performed: Organoid‑guided drug selection has shown early promise in other tumor types and anti‑HER2 ADCs are effective in some HER2‑positive cancers, but using organoid sensitivity to guide anti‑HER2 ADCs in bladder cancer is relatively novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

* 1\. Age 18-80 years, any gender; 2. All bladder cancer patients to be included in the study must meet the inclusion criteria in item 3 regarding staging, and tumor biopsy tissue taken before ADC treatment will be used for organoid culture; 3. Patients with unresectable locally advanced (cT4b and/or N2-3) or metastatic bladder cancer (M1) who have failed platinum-based chemotherapy; 4. Patients who have shown disease progression after at least one round of platinum-based chemotherapy, or have no satisfactory alternative treatment options; 5. Patients who can tolerate adverse reactions from ADC drug enfortumab vedotin treatment; 6. ECOG performance status score of 0-2; 7. Judged by the investigator to be able to comply with the trial protocol, have good adherence, cooperate in monitoring adverse events and efficacy, and participate in follow-up; 8. Voluntarily participate in this clinical trial, understand the study procedures, and have signed the informed consent form for participation.

Exclusion Criteria:

* 1\. Patients with locally advanced or metastatic bladder cancer who have not previously received platinum-containing chemotherapy; 2. Individuals with immunodeficiency or impairment (e.g., patients with AIDS, or those using immunosuppressants or undergoing radiotherapy); 3. Participants known to be allergic to the investigational drug, similar drugs, or excipients, or those with allergic constitution; 4. Individuals on long-term steroid medication or with a history of drug abuse or dependence; 5. Those who are planning to become pregnant, are currently pregnant, or are breastfeeding; 6. Individuals with abnormal blood routine, liver and kidney function, or coagulation indicators (considered abnormal if one or more of the following are met):

  1. Absolute neutrophil count (ANC) ≤ 1.5 × 10⁹/L;
  2. White blood cell count (WBC) ≤ 3.0 × 10⁹/L;
  3. Platelet count (PLT) ≤ 90 × 10⁹/L;
  4. Hemoglobin (HB) ≤ 90 g/L;
  5. Total bilirubin (TBIL) ≥ 1.5 × the upper limit of normal (ULN) of the institution;
  6. Estimated glomerular filtration rate (eGFR) ≤ 30 ml/min/1.73m²;
  7. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≥ ULN (except for patients receiving anticoagulant therapy, if considered clinically acceptable by the investigator); 7. Participants with other factors that may cause the study to be prematurely terminated, including:

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  1. History or current diagnosis of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML);
  2. History of clear neurological or psychiatric disorders, including epilepsy or dementia;
  3. Severe comorbidities that endanger patient safety or affect study completion (e.g., severe hypertension, diabetes, thyroid disorders);
  4. Other serious diseases requiring concomitant treatment, with severe laboratory abnormalities;
  5. Other serious diseases accompanied by family or social factors that could impact participant safety, or the collection of data and samples;
  6. Uncontrolled comorbid conditions, including but not limited to persistent or active infections requiring treatment, symptomatic congestive heart failure, unstable angina, or arrhythmias; 8. Participants deemed unsuitable for this study by the investigator.

Where this trial is running

Jinan, Shandong

• Qilu Hospital of Shandong University — Jinan, Shandong, China (RECRUITING)

Study contacts

• Study coordinator: Jun Chen

Conditions: Bladder Cancer, Organoid