Sasanlimab for Bladder Cancer

(CREST Trial)

Recruiting at 222 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: Chemotherapy, Immunotherapy, Immunostimulatory agents

Disqualifiers: Muscle-invasive cancer, Metastatic cancer, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Induction period: 6 weeks; Maintenance period: up to 60 months

1070 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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. This study is seeking participants whose bladder cancer is still in early stages, has not spread outside of the bladder, has been removed with surgery, and is high risk (Part A) or was previously treated with BCG (Bacillus Calmette Guerin), a standard treatment for bladder cancer (Part B). In Part A (enrollment closed), each participant was assigned to one of three study treatment groups. * One group is given sasanlimab and BCG at the study clinic. * The second group is given sasanlimab and BCG at the study clinic. This group will receive BCG for the first six weeks only. * The third group is given BCG only and will not receive sasanlimab. In Part B of the study, each new participant will be assigned to a study treatment group based on the type of their bladder tumor. - Both groups will be given sasanlimab at the study clinic. On August 31, 2022, the Sponsor announced the discontinuation of enrollment to Part B. The decision to discontinue enrollment to Part B was not made for safety reasons.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude participants who have had certain types of chemotherapy or immunotherapy recently. It's best to discuss your specific medications with the trial team.

What makes the drug Sasanlimab unique for treating bladder cancer?

Sasanlimab is unique because it is a PD-1/PD-L1 inhibitor, a type of immunotherapy that helps the immune system recognize and attack cancer cells, which is different from traditional chemotherapy that directly targets cancer cells. This approach is particularly beneficial for patients who cannot tolerate standard platinum-based chemotherapy. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Sasanlimab for bladder cancer?

Research shows that drugs similar to Sasanlimab, which block a protein called PD-L1, have been effective in treating bladder cancer. These drugs help the immune system recognize and attack cancer cells, and have shown promising results in patients who cannot tolerate traditional chemotherapy. ^{1 2 6 7 8}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for people with early-stage bladder cancer that hasn't spread, was surgically removed, and is high risk. Participants must have had BCG treatment but can't join if they've had prior radiation to the bladder, muscle-invasive or advanced cancer, certain other treatments like immunotherapy, or participated in part A of this study.

Inclusion Criteria

My bladder cancer is high-risk, not invasive, and didn't respond to BCG therapy.

I had all my bladder tumors surgically removed recently.

My bladder cancer is mainly transitional cell type and considered high risk.

Exclusion Criteria

My cancer has spread beyond the bladder lining or is in advanced stages.

I have previously received immunotherapy targeting PD-1, PD-L1, PD-L2, or CTLA-4.

I have previously been treated with immune-stimulating drugs like IL-2 or interferon.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-06801591 in combination with Bacillus Calmette-Guerin (BCG) or BCG alone, depending on the assigned group

Induction period: 6 weeks; Maintenance period: up to 60 months

Regular visits at the study clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Sasanlimab

Trial Overview The study tests sasanlimab's safety and effects on non-muscle invasive bladder cancer. It has two parts: Part A (closed) compared sasanlimab plus BCG against BCG alone; Part B assigns new participants based on tumor type to receive sasanlimab at the clinic.

How Is the Trial Designed?

Group I: PF-06801591 + BCG induction only Experimental Treatment 2 Interventions

PF-06801591 in combination with Bacillus Calmette Guerin (induction only).

Group II: PF-06801591 + BCG induction and maintenance Experimental Treatment 2 Interventions

PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).

Group III: BCG Unresponsive NMIBC Experimental Treatment 1 Intervention

PF-06801591

Group IV: BCG Unresponsive CIS Experimental Treatment 1 Intervention

PF-06801591

Group V: BCG induction and maintenance Active Control 1 Intervention

Bacillus Calmette Guerin (induction and maintenance).

Who Is Running the Clinical Trial?

Pfizer

Lead 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

The introduction of PD-L1/PD-1 inhibition therapy has significantly changed treatment strategies for advanced urothelial bladder cancer, showing efficacy in both first-line and second-line treatment settings.

Despite the promise of PD-L1/PD-1 therapies, the proportion of patients who actually benefit from these treatments remains low, highlighting the need for better biomarker-driven approaches to improve patient selection and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma. Yu, WB., Rao, JY.[2020]

MPDL3280A, an anti-PD-L1 antibody, shows significant activity in treating metastatic urothelial bladder cancer (UBC), with rapid responses often observed within 6 weeks, particularly in patients with PD-L1-positive tumors.

The treatment has a favorable safety profile, lacking renal toxicity, making it potentially more tolerable for older patients with UBC who may have renal impairment compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Powles, T., Eder, JP., Fine, GD., et al.[2022]

Neoadjuvant chemotherapy has been shown to improve overall survival in patients with locally advanced muscle-invasive bladder cancer, but its use in clinical practice remains low due to ongoing controversies regarding adjuvant chemotherapy.

Recent advancements include the approval of atezolizumab, a checkpoint inhibitor, for metastatic bladder cancer, alongside other promising therapies targeting mutational signatures, such as VEGF and HER2-directed agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. Aragon-Ching, JB., Trump, DL.[2017]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. [2017]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in urothelial bladder carcinoma. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Focus on Biochemical and Clinical Predictors of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma: Where Do We Stand? [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

A meta-analysis of the efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors as treatments for metastatic bladder cancer. [2023]