Enfortumab Vedotin + Pembrolizumab + Radiotherapy for Bladder Cancer

Recruiting in Palo Alto (17 mi)

Overseen byVadim S Koshkin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of California, San Francisco

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase Ib/II trial studies the side effects, best dose, and effectiveness of enfortumab vedotin (EV) in combination with pembrolizumab and radiation therapy for treating patients with muscle invasive bladder cancer. Standard of care treatment for muscle invasive bladder cancer is chemotherapy, to shrink the tumor before the main treatment is given (neoadjuvant), followed by surgery to remove all of the bladder as well as nearby tissues and organs (radical cystectomy). In cases where patients are not candidates for the standard of care approach or prefer a bladder sparing option, tri-modality therapy with transurethral resection of bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy is used. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer.

Research Team

Vadim S Koshkin, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for patients with muscle invasive bladder cancer. It's suitable for those who can't undergo or prefer not to have the standard treatment of chemotherapy followed by surgery. Participants should be able to receive radiation therapy and have no conditions that would interfere with the study drugs.

Inclusion Criteria

INR OR PT <= 1.5 × upper limit of normal; aPTT <= 1.5 × upper limit of normal

Ability to understand and sign a written informed consent document

HCV infection eligible if HCV viral load undetectable at screening

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Exclusion Criteria

I have not received a live vaccine in the last 30 days.

Absence of urothelial histology in TURBT tumor sample

Hypersensitivity to pembrolizumab or enfortumab vedotin or their excipients

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Treatment Details

Interventions

Enfortumab Vedotin (Monoclonal Antibodies)
Intensity Modulated Radiation Therapy (IMRT) (Radiation)
Pembrolizumab (Monoclonal Antibodies)

Trial OverviewThe trial tests a combination of enfortumab vedotin (EV) and pembrolizumab with intensity-modulated radiation therapy (IMRT). EV is an antibody-drug conjugate targeting tumor cells, while pembrolizumab is an immunotherapy that may help the immune system attack cancer.

Participant Groups

4Treatment groups

Experimental Treatment

Group I: Dose Level 3: 1.25 mg/kg Enfortumab VedotinExperimental Treatment8 Interventions

Participants receive 1.25 mg/kg enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.

Group II: Dose Level 2: 1.0 mg/kg Enfortumab VedotinExperimental Treatment8 Interventions

Participants receive 1.05 mg/kg enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.

Group III: Dose Level 1: 0.75 mg/kg Enfortumab Vedotin (Starting Dose)Experimental Treatment8 Interventions

Participants receive 0.75 mg/kg enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.

Group IV: Dose Expansion; Recommended Phase 2 Dose (RP2D)Experimental Treatment8 Interventions

Participants receive RP2D of enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.