Safety and Antitumor Activity of PF-08634404 Alone or with Enfortumab Vedotin in Adults with Locally Advanced or Metastatic Urothelial Cancer

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What is this study about?

The study focuses on adults with Urothelial Cancer that is locally advanced or has spread to other parts of the body (metastatic). Participants receive either the investigational medicine PF-08634404 alone or together with the approved therapy Enfortumab Vedotin. Both medicines are given by an IV infusion, which means they are delivered directly into a vein.

The purpose of the study is to learn how well the new medicine works against the cancer and how safe it is for patients, both by itself and when combined with the other drug. Participants will attend regular visits where they receive the infusion in a series of treatment cycles, and doctors will check for any side effects and whether the cancer is responding.

Throughout the study, doctors will monitor participants for common side effects, track any changes in the size of the cancer, and take blood samples to understand how the medicine moves through the body. The overall goal is to find a dose that is effective while keeping side effects manageable.

1 baseline assessments

after joining the study, the patient undergoes initial medical examinations, laboratory tests, and imaging studies to document the extent of locally advanced or metastatic urothelial cancer.

the purpose of these assessments is to establish a reference point for later comparison of safety and antitumor activity.

2 first treatment cycle

the patient receives an infusion of pf-08634404. the specific dose, frequency, and duration are determined by the study protocol and are not detailed in the provided information.

if the patient is assigned to the combination group, an infusion of enfortumab vedotin is given together with pf-08634404.

3 safety monitoring during cycle 1

the patient is observed for any adverse events, including dose‑limiting toxicities, which are evaluated during the first cycle.

blood samples are collected to measure drug concentrations and to assess laboratory values.

4 subsequent treatment cycles

the patient continues to receive the assigned infusion(s) in repeated cycles according to the study schedule.

each cycle includes safety assessments, laboratory tests, and imaging to evaluate tumor response.

the study records antitumor activity and pharmacokinetics (how the drug moves through the body) throughout the treatment period.

5 dose optimization and expansion (combination cohort)

for patients receiving the combination of pf-08634404 and enfortumab vedotin, the study includes a dose‑optimization phase followed by an expansion phase to identify a recommended dose.

the patient continues to be monitored for safety, tolerability, and antitumor activity during this phase.

6 treatment conclusion and final evaluation

treatment ends when the study protocol specifies, such as after a predefined number of cycles, disease progression, or unacceptable toxicity.

the patient undergoes final assessments to document overall safety, antitumor response, and any lasting side effects.

Who Can Join the Study?

You must be 18 years old or older (or meet the minimum age required by local laws) when the screening takes place.
You need a confirmed diagnosis of locally advanced or metastatic urothelial cancer that cannot be removed by surgery. This confirmation is done by looking at a tissue sample under a microscope (histologically documented) and the cancer is considered unresectable. For Cohort A the cancer must have been treated before; for Cohort B it must be untreated.
The cancer must be measurable on scans using a standard set of rules called RECIST 1.1, which defines how doctors measure tumor size. If you had radiation before, the measurable tumor must be outside the radiation area or clearly getting worse.
You must have enough tumor tissue available for laboratory studies, such as a paraffin‑embedded block or microscope slides taken from a core or surgical biopsy. Samples like fine‑needle aspiration cell blocks, cytology specimens, or bone biopsies are not acceptable.
Prior treatment rules depend on the study group:
- For Cohort A: You may have had up to three previous rounds of systemic therapy (treatment that travels through the whole body). Your most recent treatment cannot be an immune checkpoint inhibitor unless the cancer grew back more than 6 months after stopping that drug. Previous chemotherapy that contains platinum is allowed.
- For Cohort B: You must not have received any systemic therapy for this cancer. Earlier chemotherapy or immunotherapy given around the time of curative surgery (called neoadjuvant, adjuvant or perioperative therapy) is allowed only if the cancer returned more than 12 months after that treatment.
Your overall health level must be good, measured by an ECOG performance status score of 0 or 1. A score of 0 means fully active; a score of 1 means you are able to do light work but may be unable to do strenuous activities.
You need adequate organ function and blood counts as defined by the study, and you must not have received blood transfusions or medicines that boost blood cell production (such as growth factors) in the 7 days before the screening lab tests.
You must sign a written informed consent form, showing that you understand the study and agree to take part.

Who Cannot Join the Study?

Serious medical or mental health problems, including recent thoughts of suicide or lab test results that could make the study unsafe.
Active bleeding problems such as recent stomach bleeding, coughing up blood, or frequent nosebleeds that are more than minor.
Recent serious stomach or intestinal issues like severe ulcers, holes in the gut, infections, or major bleeding within the past six months.
Unhealed wounds that the doctor thinks are still significant.
Active infections including:
- Being treated with antibiotics, antivirals, or antifungals for a current infection.
- HIV infection that is not well‑controlled (CD4 count ≤200 or viral load ≥400 copies/mL).
- Hepatitis B surface antigen positive.
- Active hepatitis C infection (positive PCR test).
- Active tuberculosis or suspected TB.
History of weakened immune system (immunodeficiency).
Severe allergy to any part of the study drug or to similar antibody medicines.
Previous organ or stem‑cell transplant.
For Cohort B only: Active eye infection (keratitis) or corneal ulcers, or moderate to severe nerve problems (sensory or motor neuropathy grade 2 or higher).
Recent cancer treatments that could interfere, such as:
- Radiation to the lungs within the last six months.
- Palliative local therapy to non‑target tumors within two weeks.
- Immune‑modulating drugs (like interleukin, interferon, tumor necrosis factor) within two weeks.
- Previous anti‑VEGF therapy.
Prior use of PD‑(L)‑1 immunotherapy with:
- Severe immune‑related side effects (grade 3 or higher) except hormone‑related ones.
- Heart problems caused by immunotherapy (grade 2 cardiotoxicity).
- Any nerve or eye problems from immunotherapy.
- Side effects that have not fully resolved to mild (grade 1) before screening.
- Need for strong immune‑suppressing drugs beyond steroids.
Active brain or spinal cord tumors (including leptomeningeal spread) or compression. Treated brain metastases may be allowed only if stable for at least 14 days, off steroids for 7 days, and very small (<1 cm) without symptoms.
High risk of bleeding or fistula formation due to tumor location near major blood vessels or organs, or tumor causing large cavities.
Other recent cancers diagnosed within the past three years, unless they are very low‑risk (e.g., non‑melanoma skin cancer, early‑stage prostate cancer).
Unresolved side effects from previous cancer therapy that are worse than mild (grade 0‑1), except hair loss.
Active autoimmune disease that needed strong medication (disease‑modifying drugs, high‑dose steroids, or other immune suppressants) in the past two years. Simple hormone replacements (like thyroid or insulin) are allowed.
Serious lung conditions such as:
- Previous drug‑induced lung inflammation (ILD) or pneumonitis that required steroids or is currently active.
- Severe asthma, COPD, or lung embolism that needed high‑dose steroids or oxygen.
- Autoimmune lung disease (e.g., rheumatoid lung, sarcoidosis).
Uncontrolled major health problems within the past six months, including:
- Unstable chest pain (angina) or recent heart attack.
- Significant heart rhythm problems or a very long QT interval on an ECG (>480 ms).
- Recent stroke, mini‑stroke, or brain bleed.
- Severe heart failure (class III‑IV).
- Advanced liver cirrhosis or severe kidney disease (nephrotic syndrome).
- Uncontrolled diabetes (HbA1c ≥8 % or symptoms with 7‑8 %).
- Very high blood pressure (≥160/100 mm Hg) or hypertension crisis.
- Major blood vessel disease (e.g., large aortic aneurysm) or serious clotting events.
Recent major surgery or serious injury within four weeks, or planned major surgery during the study; even minor procedures within three days are excluded.
Use of blood‑thinning medicines (anticoagulants or thrombolytics) within ten days, unless doses are stable and blood tests (INR or aPTT) are in the therapeutic range. Regular low‑dose aspirin is allowed.
Use of antiplatelet drugs (like aspirin, ibuprofen, naproxen, clopidogrel) within seven days, except a daily low‑dose aspirin (≤325 mg).
Recent live vaccines given within four weeks or planned during the study.
High‑dose steroids or other immune suppressants (more than 10 mg prednisone daily) or conditions requiring them.
Prohibited medications taken within 21 days before the first dose, or inability to follow required medication rules.
Recent investigational product (experimental drug or vaccine) given within 30 days or five drug half‑lives, whichever is longer, or participation in another trial during this study.
Pregnancy or breastfeeding, or unwillingness to use effective birth control (for women of child‑bearing potential and men).
Study staff or their families who are directly involved in the trial.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

No sites found in this category

Other Sites

Site Name	City	Country
Netherlands Cancer Institute	Amsterdam	The Netherlands
Virgen del Rocío University Hospital	Sevilla	Spain
Hospital Universitario 12 De Octubre	Madrid	Spain
Hospital Del Mar	Barcelona	Spain
Hkbqtifa Vaxz ddfyiuxs	Barcelona	Spain
Hpgchjnj Dc Lm Slhnm Ciyq I Sgjp Pfa	Barcelona	Spain
Hbasdlcc Uazduwsxrzcne Miqkymz Dm Vxdyinpxbk	Santander	Spain

Trial status

Country	Status	Recruitment Start
Spain	Not yet recruiting	20.05.2026
The Netherlands	Not yet recruiting	20.05.2026

Trial locations

Investigated drugs:

Enfortumab Vedotin

Enfortumab Vedotin is a medication that targets cancer cells in the bladder and urinary tract. It is given by an IV infusion and works by attaching to a protein on the surface of cancer cells, delivering a toxin that helps kill those cells. In this study, it is used together with the experimental drug PF‑08634404 to see if the combination improves safety and how well it fights the cancer in participants who have not been treated before.

PF‑08634404 is a new, experimental medicine being tested for the first time in people with advanced bladder cancer. It is given by an IV infusion. The trial looks at two ways of using it: alone (monotherapy) in participants whose cancer has already been treated, and together with Enfortumab Vedotin in participants who have not received prior therapy. The study aims to find out how safe the drug is, how well the body processes it, and whether it can shrink or stop the cancer from growing.

Urothelial carcinoma – Urothelial carcinoma is a cancer that begins in the lining (urothelium) of the bladder, ureters, urethra, or renal pelvis. When the disease is locally advanced, the tumor has grown beyond the inner lining into surrounding muscle or nearby organs. In the metastatic stage, cancer cells have entered the bloodstream or lymphatic system and form new tumors in distant parts of the body such as bones, liver, or lungs. The disease typically progresses from a superficial lesion to deeper invasion and then to spread to other sites. Patients may experience increasing urinary symptoms as the tumor enlarges and spreads.

Trial ID:

2025-523523-21-00

Protocol code:

C6461006

Trial Phase:

Human Pharmacology (Phase I) – Other

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Safety and Antitumor Activity of PF-08634404 Alone or with Enfortumab Vedotin in Adults with Locally Advanced or Metastatic Urothelial Cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?