Symbiotic-GU-06-A Study to Learn About the Study Medicine PF-08634404 Alone or In Combination With Enfortumab Vedotin in Adult Participants With Locally Advanced or Metastatic Urothelial Cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Safety, Pharmacokinetic

Cohort A: •To determine the antitumor activity of PF-08634404 as monotherapy in participants with previously treated LA/mUC
•To evaluate the safety and tolerability of PF-08634404 as monotherapy in participants with previously treated LA/mUC

Cohort B: •To evaluate safety and tolerability of PF-08634404 in combination with EV (Part 1) in participants with previously untreated LA/mUC
•To characterize the overall safety profile and tolerability of PF-08634404 in combination with EV in participants with previously untreated LA/mUC
•To determine the antitumor activity of PF-08634404 in combination with EV in participants with previously untreated LA/mUC
•To identify a recommended dose for PF-08634404 in combination with EV from dose optimization/expansion (Part 2)

Secondary objectives 8

1. Cohort A: To determine additional efficacy measures of PF- 08634404 as monotherapy in participants with previously treated LA/mUC
2. To evaluate additional measures of safety and tolerability of PF-08634404 as monotherapy in participants with previously treated LA/mUC
3. To assess the PK of PF-08634404 as monotherapy in participants with previously treated LA/mUC
4. To assess the immunogenicity of PF-08634404 as monotherapy in participants with previously treated LA/mUC
5. Cohort B: To evaluate additional efficacy measures of PF- 08634404 in combination with EV in participants with previously untreated LA/mUC
6. To evaluate additional measures of safety and tolerability of PF-08634404 in combination with EV in participants with previously untreated LA/mUC
7. To assess the PK of PF-08634404 in combination with EV in participants with previously untreated LA/mUC
8. To assess the immunogenicity of PF-08634404 in combination with EV in participants with previously untreated LA/mUC

Conditions and MedDRA coding

Locally Advanced or Metastatic Urothelial Cancer

Regulatory references

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening.
2. 2. Histologically documented, unresectable LA/mUC according to RECIST 1.1. For Cohort A: Previously treated LA/mUC For Cohort B: Previously untreated LA/mUC
3. 3. Measurable disease based on RECIST 1.1 per investigator. Participants with prior definitive radiotherapy must have measurable disease per RECIST 1.1 that is outside the radiation field or have unequivocal progression of previously irradiated lesions.
4. 4. Have sufficient tumor tissue available for correlative studies, either paraffin block or slides from a core or excisional biopsy (FNA cell blocks, cytology samples and biopsies containing bone are not adequate).  See Central Laboratory Manual for tissue specifications, handling, and shipping instructions.  If less than the requested number of slides as outlined in the laboratory manual are available, the sponsor must be contacted to determine if available slides are sufficient.  If sufficient archival tissue is not available, a new baseline tumor biopsy with adequate tissue is required, unless medically infeasible and with prior agreement with the medical monitor.
5. 5. The inclusion criteria related to prior therapy are specific to the cohorts:  For Cohort A: o Up to 3 prior lines of systemic therapies are allowed for LA/mUC o Immediate prior line of therapy must not include an immune checkpoint inhibitor, unless disease progression occurred >6 months after immune checkpoint inhibitor discontinuation o Prior platinum-containing chemotherapy is allowed  For Cohort B: o No prior systemic therapy for LA/mUC is allowed o Prior systemic therapies such as neoadjuvant, adjuvant, or perioperative chemotherapy, as well as EV or immune checkpoint inhibitor, is permitted when administered in conjunction with radical surgery with curative intent (recurrence must happen >12 months after completion of therapy to be eligible)
6. 6. ECOG PS score of 0 or 1.
7. 7. Adequate organ function as defined in the following table within 7 days of first dose of study intervention:  Participants must meet the hematologic criteria below without the use of transfusions or growth factors (platelet or red blood cell transfusions, TPO, EPO, G-CSF, IL-11, etc) within 7 days prior to screening laboratory tests.
8. 8. The participant must provide written informed consent.

Exclusion criteria 23

1. 1. Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
2. 2. Participants with known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be enrolled if all of the following are met:  CNS metastases have been clinically stable with no evidence of clinical or radiographic disease progression for ≥14 days after completion of definitive radiotherapy and/or surgery and prior to study intervention.  The participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention.  Participants with asymptomatic brain metastases of longest diameter <1 cm permitted if all of the following criteria are met: o absence of neurological symptoms, o no need for corticosteroids, and o brain metastasis has no evidence of edema or haemorrhagic features
3. 3. Clinically significant risk of haemorrhage or fistula including but not limited to the following: • Significant tumor necrosis or cavitation, • The investigator deems that participation in the study poses a risk of haemorrhage; • Tumor invasion or compression of surrounding critical organs (such as aorta, heart and pericardium, superior vena cava, trachea, and esophagus) or a risk of developing tracheoesophageal or pleuroesophageal fistula; • Mediastinal lymph node metastasis with invasion of the trachea or main bronchi. If centrally located mediastinal masses are identified by imaging within 21 days excluded. • Has radiographic evidence of major blood vessel invasion/infiltration, eg, main pulmonary artery, left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta. Note: The degree of proximity to major blood vessels should be considered because of the potential risk of haemorrhage associated with tumor shrinkage/necrosis following study intervention.
4. 4. Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year OS ≥90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
5. 5. Unresolved toxicities from prior antitumor therapy, that did not recover to NCI CTCAE v5.0 Grade 0 or 1, or to levels specified in the inclusion/exclusion criteria, with the exception of alopecia. Participants who experience irreversible toxicity that is not expected to worsen with continued administration of the study intervention (eg, hearing loss) may be enrolled in the study after consultation with the medical monitor. Participants with long-term toxicity from radiotherapy that is deemed irreversible by the investigator may be enrolled in the study after consultation with the medical monitor.
6. 6. Participants with active autoimmune diseases requiring systemic treatment within the past 2 years (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs):  Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic disease modifying treatment and is allowed.  Participants with vitiligo, psoriasis, type 1 diabetes mellitus (if not excluded per exclusion criterion 8), or resolved childhood asthma/atopy are allowed.  Participants requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections are allowed (if not excluded per exclusion criterion 8).  Participants with Sjögren’s syndrome are allowed (if not excluded per exclusion criterion 7)
7. 7. Participants with any of the following respiratory conditions:  Evidence of non-infectious or drug-induced ILD or pneumonitis that: o Was previously diagnosed and was managed with parenteral steroids for any duration or oral steroids for >6 weeks, or o Had onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or o Is currently diagnosed and managed with systemic therapy, or o Is suspected on radiologic imaging at screening. o Participants who are asymptomatic and have radiographic findings of noninfectious, radiation-induced, or drug-induced ILD or pneumonitis confined to 1 bronchopulmonary segment or <10% of lung parenchyma may be enrolled after consultation with the medical monitor.  Any Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to: o Severe asthma requiring systemic corticosteroids within 30 days prior to first dose of study intervention or not well controlled with low-dose inhaled corticosteroids/long-acting beta-2 agonists. o Severe chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids. o Clinically severe and/or Grade 4 pulmonary emboli within 3 months of the first dose of study intervention. Pulmonary emboli in main or lobar pulmonary arteries are also excluded. For thromboembolic events other than pulmonary emboli please refer to exclusion criterion 8. o Any autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc).
8. 8. History of uncontrolled comorbidities within 6 months prior to the first dose including: • Unstable angina • Myocardial infarction • Uncontrolled or significant arrhythmia (including sustained ventricular tachyarrhythmia and ventricular fibrillation), untreated serious conduction system anterior or posterior hemiblock], 3rd degree AV block) • Baseline QTcF interval > 480 msec If QTcF exceeds 480 msec, the ECG is to be repeated twice and the average of the 3 QTcF values should be used to determine the participant’s eligibility. Computer-interpreted ECGs with abnormal findings must be overread by an investigator or other site physician experienced in reading ECGs before excluding participants. • Coronary/peripheral artery bypass graft • Transient ischemic attack, cerebrovascular accident, cerebral infarction (excluding lacunar infarction), or cerebral haemorrhage • Symptomatic congestive heart failure or symptoms consistent with NYHA Functional Class III or IV • Decompensated liver cirrhosis • Nephrotic syndrome • Uncontrolled diabetes defined as HbA1c ≥8.0% or HbA1c between 7.0% and 8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained (or poor compliance with hypoglycemic medications) • Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, or poor compliance with antihypertensive medications). • Significant vascular disease (such as aortic aneurysm requiring surgical repair), arterial thromboembolic event or venous thromboembolic event Grade >3 as specified in CTCAE v5.0 • Hypertensive crisis • Hypertensive encephalopathy
9. 9. Major surgery or severe trauma within 4 weeks prior to the first dose, or planned major surgery during the study; minor local surgery (excluding peripherally inserted central catheter placement and implantable central venous port placement) within 3 days prior to the first dose. Participants must have recovered adequately from the toxicity or complications from the surgery prior to starting study intervention.
10. 10. History of severe bleeding tendency or coagulation dysfunction, such as presence of clinically significant bleeding symptoms within 1 month prior to the first dose, including but not limited to gastrointestinal bleeding, haemoptysis (defined as coughing up or expectorating ≥½ teaspoon of fresh blood or small blood clots or coughing up blood without sputum; participants with blood-streaked sputum are allowed to be enrolled), or recurrent epistaxis (excluding minor nosebleeds and blood-tinged nasal discharge).
11. 11. History of esophageal varices, severe ulcers, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.
12. 12. Presence of clinically significant unhealed wounds as per investigator's judgement.
13. 13. Participants with acute, chronic or symptomatic infections including:  Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.  Known seropositivity of HIV, except for participants with controlled HIV infection on a stable regimen of ART (CD4+ count >200/mm3 and viral load of <400 copies/mL). The investigator will ensure the ART does not result in substantial interactions with study or concomitant medications.  Positive for HBV by surface antigen expression.  Active HCV infection (positive by PCR). Participants who have been treated for HCV infection are eligible if they have documented sustained virologic response 12 weeks after completion of antiviral therapy.  Testing for HIV, HBV, or HCV is not required unless mandated by local health authorities.  Participants with known active TB infection. o participants suspected of active TB are required to undergo clinical evaluation to rule out the condition.
14. 14. Participants with history of immunodeficiency.
15. 15. Known to have a history of a severe allergy to any component of the study intervention, or a history of severe allergic reaction to chimeric or humanized antibody.
16. 16. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
17. 17. Cohort B Only: Active keratitis or corneal ulcerations (Note that participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator); ongoing sensory or motor neuropathy Grade 2 or higher.
18. 18. Previous antitumor therapy including:  Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received.  Palliative local therapy for non-target lesions within 2 weeks before the first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis that would otherwise prevent trial participation.  Non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, excluding IL-11 for thrombocytopenia treatment) within 2 weeks before the first dose.  Prior exposure to anti-VEGF therapy
19. 19. For participants who have been previously exposed to PD-(L)-1 inhibitors:  History of Grade 3 or higher irAEs (excluding endocrine system-related irAEs) caused by immunotherapy, irAEs leading to permanent discontinuation of treatment, Grade 2 immune-related cardiotoxicity, or irAEs of any grade affecting the nervous system or eyes.  All adverse events from prior immunotherapy have not completely resolved or have not improved to Grade 1 before screening for this study. Participants with endocrine system-related adverse events Grade ≥2 may be enrolled if they are stable on appropriate replacement therapy and asymptomatic.  History of adverse events requiring treatment with immunosuppressants other than corticosteroids, or recurrence of adverse events during prior immunotherapy necessitating systemic corticosteroid therapy again.
20. 20. Prior and concomitant therapy: • Use of therapeutic oral or parenteral anticoagulants or thrombolytic agents within 10 days prior to the first dose (excluding use of anticoagulants as secondary prophylaxis); note: Full-dose oral or parenteral anticoagulants are permitted if the INR or aPTT is within the therapeutic range and the patient has been on a stable dose of anticoagulants for at least 2 weeks prior to the first dose. Prophylactic use of anticoagulants (for secondary prophylaxis) is permitted. • Use of chronic antiplatelet therapy, including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole, clopidogrel, or similar agents within 7 days prior to randomization. Once-daily aspirin use (maximum dose 325 mg/day) is permitted. • Use of any live or attenuated live vaccine within 4 weeks prior to the first dose, or planned vaccination of any live or attenuated live vaccine during the study • Current use of a high-dose systemic corticosteroids (>10 mg daily prednisone or equivalent) or other immune suppressant or has a condition requiring a chronic high-dose steroid or immune suppressant. • Use of any prohibited concomitant medication(s) within 21 days of the first dose of study intervention or unwillingness or inability to use a required concomitant medication(s). Refer to Section 6.9.
21. 21. Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.
22. 22. Breastfeeding participants, participants of childbearing potential, and male participants who are unwilling to follow contraceptive measures.
23. 23. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Cohort A: Confirmed ORR by investigator
2. AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study intervention
3. Cohort B: DLTs during the DLT-observation period (Cycle 1) (Part 1)
4. AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study intervention(s)
5. Confirmed ORR by investigator

Secondary endpoints 6

1. DoR by investigator
2. PFS by investigator
3. OS
4. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0)
5. Predose and postdose concentrations of PF-08634404
6. Incidence of ADA against PF-08634404

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 15

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications