Using Pembrolizumab after Tri-modality Treatment for Muscle-invasive Bladder Cancer

A Pilot Study of Pembrolizumab Monotherapy as Maintenance Therapy in MIBC Patients Who Received Bladder-Preserving Trimodally Therapy and Achieved CR

This study is testing if the drug pembrolizumab can help people with muscle-invasive bladder cancer stay cancer-free after they’ve had surgery and other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University First Hospital (Academic / other)
• Drugs / interventions: pembrolizumab, radiation, prednisone, Avelumab, chemotherapy, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05072600 on ClinicalTrials.gov

What this trial studies

This Phase II study investigates the use of pembrolizumab as a maintenance therapy for patients with muscle-invasive bladder cancer (MIBC) who have undergone maximum transurethral resection and tri-modality treatment, achieving complete response. Participants will receive pembrolizumab every 21 days for up to 17 cycles, or until disease progression or death occurs. The study aims to evaluate the effectiveness of this approach in preventing distant metastasis after tri-modality treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with muscle-invasive bladder cancer who have undergone tri-modality therapy and achieved a complete response.

Not a fit: Patients with non-urothelial carcinoma or those who have not achieved a complete response after tri-modality therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and reduce the risk of distant metastasis in patients with muscle-invasive bladder cancer.

How similar studies have performed: Previous studies have shown promising results with tri-modality treatment approaches, but the use of pembrolizumab in this specific context is novel.

Eligibility criteria

Inclusion Criteria:

1. Male/female participants who are at least 18 years of age on the day of signing informed consent.
2. Based on AJCC 8th edition: stage cT2-4N0M0，Urothelial carcinoma \>50% and

   * Requires definitive local therapy
   * Has received maximum TURBT followed by tri-modality therapy
   * Achieved CR after tri-modality therapy, the acceptable duration of time between completion of TMT and assessment of CR was 28-90 days.
3. Tumor was located at one side of bladder wall.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
5. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
7. Have adequate organ function prior to the start of study intervention.

Exclusion Criteria:

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
3. Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b disease are considered to have unresectable disease; Has any distant metastases.
4. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
5. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
6. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
9. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection.
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
19. Has had an allogeneic tissue/solid organ transplant.

Where this trial is running

Beijing, Beijing Municipality

• Peking University First Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Zhi-Song He, MD — Peking University First Hospital
• Study coordinator: Shang-Bin Qin, MD

Conditions Bladder Cancer; Bladder Neoplasms; Bladder Tumors; Urinary Bladder Cancer; Neoplasms, Bladder; bladder cancer; radiotherapy; Pembrolizumab