Neoadjuvant therapy for bladder cancer patients who can't tolerate cisplatin

Perioperative Efficacy of RC48 Combined with Toripalimab in Treatment of Cisplatin Ineligible MIBC

This study is testing a new combination of immune treatments for bladder cancer patients who can't take cisplatin to see if it helps them before surgery.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhujiang Hospital (Academic / other)
• Drugs / interventions: toripalimab, chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06341400 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining immune checkpoint inhibitors with antibody conjugate drugs as a neoadjuvant treatment for patients with muscle-invasive bladder carcinoma (MIBC) who are ineligible for or refuse cisplatin-based chemotherapy. A total of 55 patients will receive RC48-ADC and toripalimab intravenously every two weeks for four cycles before surgery and eight cycles after surgery. The primary goal is to evaluate the pathological complete response (pCR) rate, while secondary goals include assessing safety, disease-free survival, overall survival, and response rates. The study also involves collecting plasma and tumor tissue for further analysis of potential predictive biomarkers.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with muscle-invasive bladder carcinoma who are ineligible for or have declined cisplatin-based chemotherapy.

Not a fit: Patients with bladder cancer who are eligible for cisplatin-based chemotherapy or have other treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with bladder cancer who cannot tolerate standard cisplatin therapy.

How similar studies have performed: Other studies have shown promise with similar approaches using immune checkpoint inhibitors in bladder cancer, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily agree to provide written informed consent.
2. Male or female, aged ≥18 years old.
3. Patients must be ineligible for cisplatin-based chemotherapy or refuse cisplatin-based chemotherapy because of any of the following:

   Creatinine clearance (CrCl) \<60 mL/min, ECOG performance status (PS) 0-1 Creatinine clearance (CrCl) ≥ 60 mL/min, ECOG PS 2 (if the patient is eligible for RC) Hearing impairment ≥ CTCAE level 2 According to CTCAE criteria, neuropathy was ≥ grade 2 The patient declined cisplatin-based chemotherapy
4. Patients must be medically suitable for TURBT and RC.
5. Pathological examination and immunohistochemical Her-2 (≥1+)
6. measurable lesions according to RECIST 1.1.
7. Adequate organ function, as demonstrated by the following laboratory results within 7 days before study treatment:

   The heart ejection fraction was ≥50%. Hemoglobin ≥9 g/dL; Absolute neutrophil count ≥ 1.5×109 /L and platelet ≥ 100×109 /L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5×ULN.
8. All female subjects will be considered to be of reproductive potential unless they are postmenopausal or have been surgically sterilized. Female subjects of childbearing potential had to consent to the use of highly effective contraception. Male subjects of childbearing potential and their female partners had to consent to the use of highly effective contraception.
9. Be willing to comply with the study access schedule and the prohibitions and restrictions set forth in this Agreement.

Exclusion Criteria:

1. known hypersensitivity to components of recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate or allergic reaction to toripalimab.
2. toxicity from previous antineoplastic therapy did not revert to CTCAE grade 0-1 (except grade 2 alopecia).
3. pleural or abdominal effusion with clinical symptoms requiring ongoing treatment.
4. history of major surgery within 4 weeks of planned initiation of trial treatment.
5. received live virus vaccine within 4 weeks after planned initiation of trial treatment.
6. currently known active HIV or tuberculosis infection.
7. diagnosed as HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive.
8. there is history or current evidence of any condition, treatment, or laboratory abnormality that the treatment investigator believes may confound the trial results, interfere with the participant's participation throughout the trial, or be inconsistent with the participant's participation.
9. history of other malignancies within the past 5 years.
10. known central nervous system metastases
11. uncontrolled hypertension, diabetes, interstitial lung disease, or chronic obstructive pulmonary disease.
12. receiving systemic therapy (e.g., immunomodulatory agents, corticosteroids, or immunosuppressive agents) for autoimmune disease within 2 years before study treatment.
13. NYHA class III heart failure.
14. pregnancy or lactation.
15. were assessed by the investigator as unable or unwilling to comply with the requirements of the protocol.

Where this trial is running

Guangzhou, Guangdong

• Zhujiang Hospital, Southern Medical University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Abai Xu, doctor — Zhujiang Hospital
• Study coordinator: Abai Xu, doctor

Conditions Bladder Cancer; Muscle-Invasive Bladder Carcinoma; Neoadjuvant Therapy