Immunotherapy + Radiation for Bladder Cancer

(RAD-VACCINE Trial)

Overseen By Maryam Anis

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Corticosteroids, Immunosuppressants, others

Disqualifiers: Metastatic disease, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for muscle-invasive bladder cancer in individuals unable to receive standard chemotherapy. It combines the immune therapy drug Sasanlimab with targeted radiation (Stereotactic Body Radiation Therapy) to function like a vaccine against the cancer before bladder removal surgery. This approach targets patients with bladder cancer who have declined or are ineligible for cisplatin-based chemotherapy due to factors like reduced kidney function or hearing loss. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications like corticosteroids or other immunosuppressive drugs, you may need to stop them 14 days before starting the study treatment.

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

Research has shown that Sasanlimab, when combined with the BCG vaccine, may help treat non-muscle invasive bladder cancer. In these studies, researchers closely monitored the safety of Sasanlimab. Deaths occurred in 8.6% of patients, but most were unrelated to bladder cancer or the treatment, indicating that Sasanlimab is generally well-tolerated.

For Stereotactic Body Radiation Therapy (SBRT), research has found it to be a safe and effective treatment for various cancers, including those in the urinary system. One study found that 74% of bladder cancer patients were alive three years after receiving SBRT, although some experienced urinary problems.

Overall, both Sasanlimab and SBRT have been well-tolerated in past studies, with manageable side effects. This suggests these treatments have a reasonable safety profile in cancer care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining immunotherapy with radiation for bladder cancer because this approach offers a fresh way to tackle the disease. Unlike traditional treatments that often rely on surgery or chemotherapy alone, this method uses sasanlimab, an immunotherapy drug, to boost the body's own immune system to fight cancer cells more effectively. Additionally, the use of stereotactic body radiation therapy (SBRT) allows for precise targeting of tumors, potentially reducing side effects and improving outcomes. This combination aims to enhance the body's natural defenses against cancer while improving the precision and effectiveness of treatment.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

In this trial, all participants will receive a combination of sasanlimab and stereotactic body radiation therapy (SBRT), along with standard-of-care radical cystectomy. Research has shown that sasanlimab, when combined with BCG (a treatment that boosts the immune system to fight bladder cancer), can significantly improve patient outcomes. Specifically, one study found a 32% decrease in the risk of cancer progression or recurrence, highlighting sasanlimab's effectiveness in treating bladder cancer.

SBRT, another component of this treatment plan, has demonstrated positive results in similar types of cancer. In one study, 82% of patients experienced positive outcomes without disease progression. Although data for bladder cancer is limited, SBRT has proven beneficial in treating related conditions.

Combining these treatments aims to leverage their strengths to combat muscle-invasive bladder cancer effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Raj Satkunasivam, MD

Principal Investigator

Houston Methodist Hospital, Houston Methodist Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with muscle-invasive bladder cancer who can't have cisplatin chemotherapy. They need good bone marrow and kidney function, no severe infections or heart issues recently, and no history of certain autoimmune diseases or other cancers in the last 2 years. Participants must be willing to use effective contraception.

Inclusion Criteria

More than half of my cancer is urothelial carcinoma.

I can take care of myself and perform daily activities.

I am able to understand and sign the consent form.

Exclusion Criteria

I have an active heart condition.

I have had radiation therapy to my bladder before.

I have had an organ or stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of sasanlimab followed by 3 doses of stereotactic body radiation therapy

6 weeks

5 visits (in-person)

Surgery

Participants undergo radical cystectomy within 6 weeks of the last dose of sasanlimab

Within 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and quality of life

12 weeks

3 visits (in-person)

Long-term follow-up

Participants are monitored for overall survival and recurrence-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Radical Cystectomy + Pelvic Lymph Node Dissection + Urinary Diversion
• Sasanlimab
• Stereotactic Body Radiation Therapy

Trial Overview The study tests Sasanlimab (an immune checkpoint inhibitor) combined with stereotactic body radiation therapy before surgery for bladder cancer. It's a phase II trial where all participants receive this combination as a potential 'in-situ vaccine' to boost their immune response against the cancer.

How Is the Trial Designed?

Group I: Open arm Experimental Treatment 3 Interventions

All patients will receive study interventions (sasanlimab and SBRT) and standard-of-care radical cystectomy.

Radical Cystectomy + Pelvic Lymph Node Dissection + Urinary Diversion is already approved in United States, European Union for the following indications:

Approved in United States as Radical Cystectomy with Pelvic Lymph Node Dissection and Urinary Diversion for:

• Muscle-invasive bladder cancer

Approved in European Union as Radical Cystectomy with Pelvic Lymph Node Dissection and Urinary Diversion for:

• Muscle-invasive bladder cancer

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

High dose, short course preoperative radiation therapy (1,660 rad over 4 days) followed by immediate cystectomy for bladder cancer does not increase the risk of operative morbidity or mortality, making it a safe approach.

The study found that the incidence of nodal involvement in bladder cancer patients varied significantly, highlighting the importance of pelvic node treatment during cystectomy, especially for more advanced tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with high dose, short course preoperative radiation therapy and immediate single stage cystectomy in management of bladder cancer: a preliminary report. Skinner, DG., Kaufman, JJ., Tift, JP.[2006]

In a study of 148 patients who underwent radical cystectomy after receiving high-dose pelvic radiation, the early complication rate was found to be higher than in non-irradiated patients, with 335 complications reported within 90 days post-surgery.

Factors such as being over 65 years old and having a higher American Society of Anesthesiologists score were significant predictors of postoperative complications, while the type of urinary diversion did not significantly impact complication rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early complications of cystectomy after high dose pelvic radiation. Eisenberg, MS., Dorin, RP., Bartsch, G., et al.[2010]

A national population-based registry in Sweden successfully collected data on 285 out of 435 cystectomies performed in 2011, highlighting the feasibility of tracking complications and outcomes in bladder cancer surgeries.

The study found that longer operating times (over 318 minutes) and older age (76-89 years) were significantly associated with an increased risk of complications, with 36% of patients experiencing complications post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary bladder cancer treated with radical cystectomy: perioperative parameters and early complications prospectively registered in a national population-based database. Jerlström, T., Gårdmark, T., Carringer, M., et al.[2022]

Immunotherapy is becoming increasingly important in treating kidney and bladder cancers, showing promise in improving patient outcomes.

Combining immunotherapy with radiotherapy may enhance tumor response, including in cases of metastatic tumors, based on encouraging preclinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination radiotherapy-immunotherapy in genitourinary cancer]. Ollivier, L., Guimas, V., Rio, E., et al.[2021]

The RACE IT trial is investigating the safety and feasibility of combining the PD-1 inhibitor Nivolumab with radiation therapy in patients with locally advanced bladder cancer, aiming to improve treatment outcomes for those ineligible for standard chemotherapy.

The study will involve 33 patients receiving Nivolumab and radiation before undergoing radical cystectomy, with the primary goal of assessing the completion rate of this combined treatment by week 15.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer - study protocol of a prospective, single arm, multicenter phase II trial (RACE IT). Schmid, SC., Koll, FJ., Rödel, C., et al.[2020]

Patients with a history of pelvic irradiation undergoing radical cystectomy for bladder cancer tend to present with more advanced disease, as indicated by a higher proportion of T4 disease (35% vs 11% in nonirradiated patients).

Despite the more advanced disease, prior pelvic irradiation did not significantly affect bladder cancer recurrence-free survival or specific survival outcomes, suggesting that it is not a predictive factor for survival after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical Cystectomy for Bladder Cancer in Patients With and Without a History of Pelvic Irradiation: Survival Outcomes and Diversion-related Complications. Nguyen, DP., Al Hussein Al Awamlh, B., Faltas, BM., et al.[2015]

In a study of 1,054 patients treated with radical cystectomy for invasive bladder cancer, the 5-year recurrence-free survival rate was 68%, demonstrating the effectiveness of this surgical approach over a median follow-up of 10.2 years.

Patients with organ-confined, lymph node-negative tumors had significantly better outcomes, with 5-year recurrence-free survival rates reaching 92%, while those with lymph node involvement had much lower survival rates of 35%, highlighting the importance of tumor stage and lymph node status in predicting clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients. Stein, JP., Lieskovsky, G., Cote, R., et al.[2023]

In a study of five patients with node-positive bladder cancer, radical treatment including pelvic radiotherapy was well-tolerated, with only minimal gastrointestinal and urinary symptoms reported, indicating a favorable safety profile.

Local control of the disease was effective, as none of the patients experienced pelvic relapse, although two did develop distant metastatic disease, suggesting that while the treatment is promising, further research is needed to identify which patients would benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The delivery of radical radiotherapy to the bladder and pelvis in node-positive (N1) bladder cancer: a five patient case series. Fackrell, DG., Ford, D., Chetiyawardana, S., et al.[2022]

In a study of 196 patients who underwent robot-assisted radical cystectomy (RARC) for bladder cancer, 80% experienced some form of complication within 90 days post-surgery, highlighting the significant morbidity associated with this procedure.

Major complications occurred in 35% of patients, with the most common issues being infections and gastrointestinal problems, indicating that while RARC is a minimally invasive option, it still carries substantial risks that need careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardized analysis of frequency and severity of complications after robot-assisted radical cystectomy. Yuh, BE., Nazmy, M., Ruel, NH., et al.[2022]

In a study of 125 patients undergoing radical cystectomy for bladder cancer, disease-free survival (DFS) and disease-specific survival (DSS) were significantly influenced by the extent of the tumor, with 100% survival in pT0 tumors and decreasing rates in more advanced stages (pT2: 69.2% DFS, pT4: 39.5% DFS).

Lymph node involvement also impacted survival outcomes, with patients having negative lymph nodes showing a 69.4% DFS compared to 51.8% in those with lymph node metastases, highlighting the importance of timely intervention based on tumor and lymph node status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radical cystectomy in the treatment for bladder carcinoma: results of 125 operated patients]. Babjuk, M., Hanus, T., Safarík, L., et al.[2007]

In a study of 1,054 patients treated with radical cystectomy for invasive bladder cancer, the 5-year recurrence-free survival rate was 68%, demonstrating the effectiveness of this surgical approach over a median follow-up of 10.2 years.

Patients with organ-confined, lymph node-negative tumors had significantly better outcomes, with 5-year recurrence-free survival rates reaching 92%, while those with lymph node involvement had much lower survival rates of 35%, highlighting the importance of tumor stage and lymph node status in predicting clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. Stein, JP., Lieskovsky, G., Cote, R., et al.[2023]

Citations

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Pfizer's Sasanlimab Combination Significantly Improves ... Pivotal Phase 3 CREST trial results show a 32% reduction in the risk of disease-related events, including high-grade disease recurrence or ...

2. nature.com nature.com/articles/s41591-025-03738-z

Sasanlimab plus BCG in BCG-naive, high-risk non-muscle ... The CREST trial showed a statistically significant and clinically meaningful benefit for sasanlimab in combination with BCG-I+M over the SOC ( ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04165317

NCT04165317 | A Study of Sasanlimab in People With Non ... The purpose of this study is to learn about the safety and effects of the study medicine (sasanlimab) in people with non-muscle invasive bladder cancer.

4. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-bladder-cancer/160800-asco-2025-sasanlimab-in-combination-with-bcg-in-bcg-naive-high-risk-nmibc-event-free-survival-subgroup-analyses-based-on-disease-stage-from-the-crest-study.html

ASCO 2025: Sasanlimab in Combination with BCG ... Sasanlimab in combination with BCG (induction and maintenance) showed prolonged event free survival compared with BCG (induction and maintenance) in patients ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38189180/

phase III study of sasanlimab and Bacillus Calmette-Guérin ... The primary outcome is event-free survival. Secondary outcomes include additional efficacy end points and safety. The target sample size is ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40450141/

Sasanlimab plus BCG in BCG-naive, high-risk non-muscle ... Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: the randomized phase 3 CREST trial. Nat Med. 2025 Aug;31(8): ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04165317

NCT04165317 | A Study of Sasanlimab in People With Non ... The purpose of this study is to learn about the safety and effects of the study medicine (sasanlimab) in people with non-muscle invasive bladder cancer.

8. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-sasanlimab-combination-bcg-improves-event-free

Pfizer's Sasanlimab in Combination with BCG Improves ... The study met its primary endpoint of event-free survival (EFS) by investigator assessment, demonstrating a clinically meaningful and ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4610

Sasanlimab in combination with bacillus Calmette-Guérin ... Results: At data cutoff (Dec 2, 2024), 695/703 pts randomized to Arms A (n = 348) and C (n = 347) had a BL score and ≥1 post-BL score.