Pembrolizumab + Chemotherapy for Bladder and Prostate Cancer

Overseen By Sara Rodriguez

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Androgen deprivation therapy

Must not be taking: Live vaccines, Immunosuppressants

Disqualifiers: Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 15

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well pembrolizumab, a medication that helps the body fight cancer, works when combined with chemotherapy to treat certain bladder and prostate cancers. The focus is on small cell and neuroendocrine cancers that have spread beyond their original location. Participants will receive pembrolizumab along with chemotherapy drugs, including carboplatin, cisplatin, docetaxel, and etoposide. This trial might suit individuals with advanced bladder or prostate cancer who haven't previously received certain chemotherapy treatments. As a Phase 1 trial, the research aims to understand how the treatment works in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing androgen deprivation therapy and treatment for bone metastasis are allowed, and prior immunotherapy is permitted if completed more than 4 weeks before enrollment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab is usually well-tolerated by patients. Studies indicate it can improve survival rates in bladder cancer, with about 61% of patients alive three years after treatment. However, some people report side effects like tiredness and skin rash.

Carboplatin is often used to treat cancer and has proven effective, though it can cause side effects. A common one is myelosuppression, where the bone marrow produces fewer blood cells, though severe cases are rare.

Cisplatin is another chemotherapy drug that works well. It is generally well-tolerated, but about 40% of patients may experience serious side effects like low blood cell counts.

Docetaxel, approved by the FDA for prostate cancer, is usually well-tolerated. It can lower the risk of dying from prostate cancer, although side effects like tiredness and low blood cell counts can occur.

Etoposide is used for several cancers, including prostate and bladder cancer. While effective, it can cause side effects like low white blood cell count, anemia, and loss of appetite.

Overall, these treatments have been studied and are generally safe, though side effects can occur. Always consult a doctor about potential risks when considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combining pembrolizumab with chemotherapy for bladder and prostate cancer because it leverages the unique mechanism of immunotherapy. Pembrolizumab is a type of immunotherapy that works by targeting the PD-1/PD-L1 pathway, helping the immune system recognize and attack cancer cells more effectively. This is different from standard treatments, which primarily use chemotherapy to kill rapidly dividing cells. By combining pembrolizumab with platinum-based chemotherapy, the treatment aims to enhance the immune response while directly attacking the cancer, potentially leading to better outcomes for patients.

What evidence suggests that pembrolizumab with chemotherapy might be an effective treatment for bladder and prostate cancer?

Research has shown that pembrolizumab, a monoclonal antibody, may help treat certain bladder cancers. One study found that 61% of patients who received pembrolizumab were still alive after three years. In this trial, participants will receive pembrolizumab along with standard chemotherapy. Etoposide, often combined with chemotherapy drugs like cisplatin or carboplatin, can effectively treat neuroendocrine prostate cancer, sometimes significantly shrinking tumors. Cisplatin and carboplatin stop cancer growth by damaging the DNA in cancer cells. Docetaxel, another chemotherapy drug, can be effective in some cancers and may extend life when used with other treatments. Overall, combining pembrolizumab with these chemotherapy drugs might enhance their effectiveness against cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Arnold Chin

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced small cell/neuroendocrine cancers of the bladder, urethra, or prostate. Participants must have adequate organ function and no recent blood transfusions. They should not have had certain cancer treatments recently and agree to use contraception. Exclusions include active autoimmune disease, known psychiatric disorders that affect participation, recent other cancer therapies, severe allergies to trial drugs, active infections like HIV or hepatitis B/C, pregnant or breastfeeding women.

Inclusion Criteria

Platelets >= 100 000/uL within 10 days prior to the start of study treatment

Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L within 10 days prior to the start of study treatment, without erythropoietin dependency and without pRBC transfusion within the last 2 weeks

Creatinine =< 1.5 x ULN OR measured or calculated creatinine clearance (GFR can also be used) >= 30 mL/min for participants with creatinine levels >1.5 x institutional ULN within 10 days prior to the start of study treatment

Exclusion Criteria

You have an ongoing autoimmune disease that has required medication in the past 2 years.

WOCBP with a positive urine pregnancy test within 72 hours prior to receiving the first dose of trial medication

You have a mental illness or addiction that could make it difficult to follow the rules of the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and platinum-based chemotherapy. Pembrolizumab is administered IV over 30 minutes on day 1, and chemotherapy is administered according to cohort-specific regimens. Treatment repeats every 3 weeks for up to 6 courses.

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days post-treatment, then every 9-12 weeks for up to 2 years, and every 12 weeks thereafter.

Up to 3 years

Regular visits every 9-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Docetaxel
• Etoposide
• Pembrolizumab

Trial Overview The study tests pembrolizumab (an immune system booster) combined with chemotherapy drugs cisplatin, carboplatin, docetaxel, and etoposide in patients with specific urothelial/prostate cancers. The goal is to see if this combination is more effective than current treatments at stopping cancer growth by killing tumor cells or preventing them from dividing and spreading.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, platinum-based chemotherapy) Experimental Treatment 5 Interventions

Participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Participants also receive standard of care chemotherapy comprising either etoposide IV on days 1-3 and cisplatin IV or carboplatin IV on day 1 (Cohort 1), or etoposide IV on days 1-3, carboplatin IV on day 1, and docetaxel IV on day 1 (Cohort 2). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 39 patients with muscle-invasive bladder cancer, the combination of gemcitabine, cisplatin, and the immune checkpoint inhibitor pembrolizumab was effective, achieving pathologic downstaging in 56% of patients and complete pathologic response in 36%.

The treatment was generally safe, with common side effects including thrombocytopenia, anemia, and neutropenia, but no severe immune-related adverse events were reported, indicating a manageable safety profile for this neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. Rose, TL., Harrison, MR., Deal, AM., et al.[2022]

In a phase 2 trial involving 22 patients with advanced urothelial cancer who had previously failed platinum-based chemotherapy, the combination of docetaxel and ifosfamide showed an objective response rate of 25%, with 20% achieving complete responses, particularly in those with lymph node-only recurrences.

The treatment was well tolerated, with mild to moderate side effects, and serious toxicities were relatively low, suggesting that this combination therapy could be a viable option for patients with specific recurrence patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study. Krege, S., Rembrink, V., Börgermann, C., et al.[2019]

In a study of 43 patients with advanced urothelial cancer treated with pembrolizumab, 51.2% experienced immune-related adverse events (irAEs), which were linked to better survival outcomes.

Patients with grade 2 or higher irAEs had not reached median overall survival (OS) or time to treatment failure (TTF), while those with lower grade irAEs had median OS of 160 days, suggesting that the presence of irAEs may indicate a more effective response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Immune-Related Adverse Events with Pembrolizumab Efficacy in the Treatment of Advanced Urothelial Carcinoma. Kobayashi, K., Suzuki, K., Hiraide, M., et al.[2020]

In a phase 2 study involving 370 patients with advanced urothelial cancer who were ineligible for cisplatin-based chemotherapy, first-line treatment with pembrolizumab resulted in a 24% objective response rate, with 83% of these responses ongoing at a median follow-up of 5 months.

Pembrolizumab demonstrated acceptable safety, with only 10% of patients experiencing serious treatment-related adverse events, making it a viable treatment option for patients with significant comorbidities or poor prognostic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Balar, AV., Castellano, D., O'Donnell, PH., et al.[2022]

Pembrolizumab, a checkpoint inhibitor, has been shown to significantly improve overall survival in patients with locally advanced or metastatic urothelial carcinoma who have progressed after cisplatin-containing chemotherapy, compared to standard chemotherapy options.

Additionally, evidence from Phase 1 and 2 trials suggests that checkpoint inhibitors like pembrolizumab are effective as a first-line treatment for patients who cannot tolerate cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of bladder cancer. Sundahl, N., Rottey, S., De Maeseneer, D., et al.[2018]

Atezolizumab and pembrolizumab received accelerated FDA approval in 2017 for treating advanced urothelial carcinoma in patients who cannot receive cisplatin, showing objective response rates of 23.5% and 28.6%, respectively, in single-arm trials with a total of 746 patients.

Due to preliminary concerns from ongoing trials, the FDA revised the indications for these drugs, now specifying they are for patients not eligible for any platinum-based chemotherapy or those with high PD-L1 expression, ensuring a more targeted treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab or Pembrolizumab for the Treatment of Patients with Advanced Urothelial Carcinoma Ineligible for Cisplatin-Containing Chemotherapy. Suzman, DL., Agrawal, S., Ning, YM., et al.[2020]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

In the Phase III KEYNOTE-045 trial, pembrolizumab significantly improved overall survival in patients with second-line metastatic urothelial carcinoma compared to standard treatments like docetaxel, paclitaxel, and vinflunine.

Early results from the Phase II KEYNOTE-052 trial suggest that pembrolizumab is effective for first-line treatment in patients with metastatic urothelial carcinoma who are not eligible for cisplatin, leading to its FDA approval for these indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. Lundgren, KT., Farina, MS., Bellmunt, J.[2018]

In the PURE-01 study involving 50 patients with muscle-invasive bladder carcinoma, neoadjuvant treatment with pembrolizumab resulted in a pathologic complete response (pT0) in 42% of patients, demonstrating its efficacy as a pre-surgery immunotherapy.

The study found that patients with high PD-L1 expression (CPS ≥ 10%) had a significantly higher rate of pT0 (54.3%) compared to those with lower expression (13.3%), suggesting that pembrolizumab may be particularly effective in patients with PD-L1-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. Necchi, A., Anichini, A., Raggi, D., et al.[2021]

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34535437/

Overall Survival of Patients Receiving Cisplatin or ... In this study, we compared the survival benefits of cisplatin- and carboplatin-based chemotherapy for patients with metastatic bladder cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405456922000529

Reassessment of the Efficacy of Carboplatin for Metastatic ... Survival outcomes for patients with advanced or metastatic urothelial carcinoma (AMUC) are extremely poor with the overall 5-yr survival rates of only ...

3. eu-focus.europeanurology.com eu-focus.europeanurology.com/article/S2405-4569(22)00052-9/fulltext

Reassessment of the Efficacy of Carboplatin for Metastatic ... Carboplatin-based chemotherapy seems to be more effective in contemporary series than in historical controls; moreover, it offers additive ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5740837/

The combination of paclitaxel and carboplatin as second ... TC achieved an 18.7% overall response rate and a 56.2% disease control rate. Myelosuppression was the most common grade ≥3 toxicity, but no treatment-associated ...

5. academic.oup.com academic.oup.com/oncolo/article/29/11/999/7789551

Meta-analysis of platinum chemotherapy combinations with ... The meta-analysis showed that cisplatin-gemcitabine plus IO combination and carboplatin-gemcitabine plus IO combination improve progression-free survival.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7976390/

Paclitaxel and carboplatin chemotherapy after platinum- ... It revealed that the median OS was 10.9 months (95% CI, 0.9-12.7 months), the objective response rate was 28.6%, and the disease control rate was 85.7% in ...

7. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-bladder-cancer/160801-asco-2025-nivolumab-ipilimumab-versus-gemcitabine-carboplatin-chemotherapy-for-previously-untreated-unresectable-or-metastatic-urothelial-carcinoma-final-results-for-cisplatin-ineligible-patients-from-the-checkmate-901-trial.html

ASCO 2025: Nivolumab + Ipilimumab versus Gemcitabine ... The phase 3, global, open-label, randomized CheckMate 901 trial compared nivolumab + ipilimumab versus gemcitabine + carboplatin in cisplatin-ineligible ...