EV/P for Bladder Cancer

(Chrono-EVP Trial)

Not yet recruiting at 4 trial locations

Overseen By Dr. Guliz Ozgun, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Guliz Ozgun

Must be taking: Enfortumab vedotin, Pembrolizumab

Disqualifiers: Non-urothelial cancer, Concurrent malignancy, Brain metastasis, Psychiatric disorder, Sleep disorder, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether administering standard bladder cancer treatments, enfortumab vedotin and pembrolizumab (EV/P), at different times of the day affects their effectiveness and side effects. Participants will receive their treatments either in the morning or the afternoon, assigned randomly. This study targets adults with advanced bladder cancer who can adhere to a treatment schedule, either before 11:30 a.m. or after 1:30 p.m. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants an opportunity to contribute to advancing cancer treatment.

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

Research shows that the combination of enfortumab vedotin and pembrolizumab (EV/P) is generally safe for people with advanced bladder cancer. Studies have found no new safety issues, confirming it as a standard treatment option. Another study indicated that EV/P is safe even for patients with poor kidney function. Most patients can handle the side effects without major problems. Overall, the treatment has manageable side effects, making it a promising option for those considering joining a clinical trial. ^{1 2 3 4}

Why are researchers excited about this trial?

Researchers are excited about Enfortumab Vedotin and Pembrolizumab (EV/P) for bladder cancer because it offers a promising new approach by combining two powerful therapies. Enfortumab Vedotin is an antibody-drug conjugate that specifically targets cancer cells, delivering chemotherapy directly to them, while Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses against cancer and potentially improve outcomes for patients compared to traditional treatments like chemotherapy alone. Moreover, the trial also explores the optimal timing of administration, which could lead to more personalized and effective treatment schedules.

What evidence suggests that the timing of EV/P treatment could be effective for advanced bladder cancer?

Studies have shown that the combination of enfortumab vedotin and pembrolizumab (EV/P) effectively treats advanced bladder cancer. Earlier research revealed that nearly 47% of patients experienced tumor shrinkage, and about 28% saw their cancer completely disappear. Most patients can handle the side effects of this treatment well. Real-world evidence supports these findings, indicating that EV/P offers significant benefits for advanced bladder cancer. In this trial, participants will receive EV/P treatment either in the morning or afternoon to evaluate any differences in outcomes based on administration timing. This suggests that EV/P is a promising treatment option for this condition. ^{1 2 5 6}

Are You a Good Fit for This Trial?

Adults with advanced bladder cancer are eligible for this trial. The study is examining if the time of day when they receive their standard treatment affects its effectiveness or side effects. Participants will be randomly assigned to receive treatments either in the morning or afternoon and followed up for up to 24 months.

Inclusion Criteria

I am eligible for the standard EV/P treatment.

Measurable disease per RECIST 1.1

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

Inability to comply with protocol-specified infusion timing for at least the first 3 months

Night shift workers

Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements 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 enfortumab vedotin and pembrolizumab (EV/P) either in the morning or afternoon as part of their standard-of-care treatment for advanced bladder cancer

12 weeks

Visits follow standard-of-care guidelines

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin and Pembrolizumab (EV/P)

Trial Overview

The trial tests whether administering enfortumab vedotin and pembrolizumab (EV/P) at different times of day impacts treatment success in advanced bladder cancer. It compares morning administration (before 11:30am) versus afternoon (after 1:30pm), considering circadian rhythms.

How Is the Trial Designed?

Group I: Arm A: Morning EV/P Treatment Active Control 1 Intervention

Participants will receive standard-of-care therapy (Ev/P) administered in the morning (before 11:30am).

Group II: Arm B: Afternoon EV/P Treatment Active Control 1 Intervention

Participants will receive standard-of-care therapy (EV/P) administered in the afternoon (after 1:30pm).

Who Is Running the Clinical Trial?

Guliz Ozgun

Lead Sponsor

British Columbia Cancer Agency

Collaborator

Trials

181

Recruited

95,900+

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S1078143925004156

Outcomes of enfortumab vedotin plus pembrolizumab in ...

Real-world data shows that patients with poor kidney function had comparable clinical outcomes with EV+P.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41177680/

Real-World Outcomes of Enfortumab Vedotin and ...

In this real-world cohort, enfortumab vedotin-pembrolizumab combination demonstrated meaningful clinical activity and manageable toxicity in both first-line ...

3.

clinical-genitourinary-cancer.com

clinical-genitourinary-cancer.com/article/S1558-7673(25)00153-3/fulltext

Real-World Outcomes of Enfortumab Vedotin and ...

Herein, we evaluated the real-world effectiveness and safety of EV-Pembro in patients with advanced urothelial carcinoma, comparing outcomes between those who ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.745

Clinical efficacy of enfortumab vedotin-pembrolizumab (EV ...

The median follow-up time was 7.1 months (IQR: 4.93-9.26). In terms of BOR, 56 patients (46.6%) experienced PR, 34 (28.3%) CR, 12 (10%) PD, 7 ( ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.664

EV-302: Updated analysis from the phase 3 global study of ...

Results confirm durable EV+P efficacy with no new safety signals, reinforcing EV+P as SOC for the 1L treatment of pts with la/mUC.

6.

oncologynewscentral.com

oncologynewscentral.com/bladder-cancer/real-world-data-support-ev-pembrolizumab-in-advanced-urothelial-cancer

Real-World Data Support EV-Pembrolizumab in Advanced ...

In cohort A, median progression-free survival (PFS) was 12.9 months, and median overall survival (OS) was 25.1 months. In comparison, EV-302 ...