Neoadjuvant PD-1 Monoclonal Antibody in Cisplatin-ineligible High Risk Upper Tract Urothelial Carcinoma

NCT04672330 | Completed Phase 2 DMC

• 1 other identifier: NEO-IO
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant therapy of cisplatin-based chemotherapy has been proved to improve prognosis of muscle invasive UTUC patients in several studies. This study is designed to investigate the safety and efficacy of neoadjuvant PD-1 monoclonal antibody in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC) which are ineligible for cisplatin. Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The safety, tolerability, and efficacy of tislelizumab in patients with PD-L1 positive urothelial carcinoma who progressed during/following platinum-containing therapy was proved in a phase 2 trial (CTR20170071). This trial focuses on the efficacy of Tislelizumab to induce pathological down-staging of locally advanced UTUC in neoadjuvant setting.

Conditions

Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial Carcinoma

Keywords

neoadjuvant therapy; radical nephroureterectomy; Tislelizumab; Cisplatin-ineligible

Outcome Measures

Primary Outcomes (1)

• pathological reponse rate

  ypT0N0 at surgical specimen，in the intention-to-treat population

  30 days after surgery

Secondary Outcomes (5)

• pathological response rate

  30 days after surgery

• perioperative complication rate

  30 days after surgery

• objective response rate

  12 months after drug treatment

• disease free survival

  5 years after surgery or treatment

• overall survival

  5 years after enrollment

Study Arms (1)

Neoadjuvant arm

EXPERIMENTAL

Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation） Drug: Tislelizumab 200 mg per cycle, IV on day 1 of every 3-week cycle, for 2-4 cycles prior to surgery

Drug: Tislelizumab

Interventions

Tislelizumab DRUG

Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) before surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation）

Also known as: anti-PD-1 monoclonal antibody

Neoadjuvant arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. had non-metastatic high risk UTUC and planed to receive surgery(defined as high grade UTUC either by endoscopic biopsy or urinary cytology and/or any invasive aspect on radiological examination and/or hydronephrosis );
• \. were ineligible for cisplatin-based chemotherapy(defined as meeting at least one of the following criteria: Eastern Cooperative Oncology Group \[ECOG\] performance status 2, creatinine clearance 30-60 mL/min, grade ≥2 audiometric hearing loss, grade ≥2 peripheral neuropathy, or New York Heart Association Class III heart failure);
• \. had not received any systemic anti-tumor therapy;
• \. Adequate organ function defined by study-specified laboratory tests; Hemoglobin ≥90 g/L; Hematological Absolute neutrophil count (ANC) ≥1.5×109 /L; Platelets ≥100×109 /L
• \. No functional organic disease: T-BIL≤1.5×upper limit of normal (ULN); ALT andAST≤2.5×ULN; Serum creatinine≤2×ULN; endogenous creatinine clearance rate\>30ml/min
• \. Agree to comply with scheduled visits, treatment plans, lab tests and any other required study procedures;

You may not qualify if:

• \. Patients who have received prior therapy of an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody;
• \. Patients who are allergic to monoclonal antibodies or any of its excipients;
• \. Patients who have received other systems for anti-tumor treatment (e. g., Steroid therapy, immunotherapy) within 4 weeks or enrolled in other clinical trials;
• \. Patients who are pregnant or breastfeeding, or expecting to conceive;
• \. Patients who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies);
• \. Patients who have known active Hepatitis B or Hepatitis C;
• \. Patients who have active autoimmune disease that has required systemic treatment in the past 2 years;
• \. Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment;
• \. Patients who have received prior radiation therapy to the bladder;
• Patients who have muscle invasive bladder cancer;
• Patients who have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• Patients who have a history of substance abuse or with a history of mental disorders;
• Patients who had other malignant tumors in the past five years that have not recovered except for curable tumors that have been cured including basal or squamous skin cancer, localized carcinoma in situ of the cervix or the breast and low-risk prostate cancer, etc.
• Patients who have active tuberculosis;
• Patients who have other serious and uncontrollable accompanying diseases that may affect compliance or interfere with the interpretation of results including active opportunistic infections or advanced (severe) infections, uncontrollable diabetes, cardiovascular disease (grade III or IV heart failure defined by the New York Heart Association classification, II degree atrioventricular block and above, myocardial infarction in the past 6 months, unstable arrhythmia or instability angina, cerebral infarction within 3 months, etc.) or lung disease (interstitial pneumonia, history of obstructive lung disease and symptomatic bronchospasm);

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Shanghai Renji Hospital

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (1)

• Huang J, Cai X, Ng C, Luo Y, Chen Q, Wang Z, Qiao K, Kong W, Zhang J, Chen Y, Zhang W, Zhang J, Zhang D, Wu G, Chen H, Xue W. A Phase 2 Study of Tislelizumab as Neoadjuvant Treatment of Cisplatin-Ineligible High-Risk Upper Tract Urothelial Carcinoma. J Urol. 2025 Jun;213(6):739-752. doi: 10.1097/JU.0000000000004475. Epub 2025 Feb 25.

  PMID: 39999445 DERIVED

MeSH Terms

Interventions

tislelizumab; spartalizumab

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation）

Study Record Dates

• First Submitted: December 12, 2020
• First Posted: December 17, 2020
• Study Start: December 1, 2020
• Primary Completion: January 25, 2023
• Study Completion: November 25, 2023
• Last Updated: January 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)