C6001001 - A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI-TUMOR ACTIVITY OF PF-08052667 AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 18 YEARS OF AGE AND OLDER WITH BLADDER CANCER
Date de révision : 01/05/2026
11 participants
Homme Femme
A partir de 18 ans
Critères :
Critères d'inclusion :
- 18 years of age or older (or the minimum age of consent in accordance with local regulations) at the time of signing the informed consent. *Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.
- A histologically confirmed diagnosis of high-risk, non-muscle invasive urothelial carcinoma of the bladder defined according to the World Health Organization grading system as carcinoma in situ (CIS), with or without concurrent T1/Ta papillary disease. Note: High-grade T1/Ta papillary disease, in the absence of CIS, may be eligible for certain cohorts in Part 2 and 3.
- Complete resection of all Ta/T1 papillary disease and resection or fulguration of all CIS, as feasible/applicable (the same modality of light source must be used for diagnosis and disease assessment in the study), with most recent positive TURBT occurring within 12 weeks prior to initiation of study intervention. A second TURBT must have been performed if indicated according to the current locally applicable guidelines, e.g., American Urological Association, European Association of Urology. The resection site for T1 disease must undergo biopsy evaluation of the prior resection site, 2 to 8 weeks before the initiation of study intervention, if applicable. Local urine cytology at screening must be negative for high-grade urothelial carcinoma in participants with papillary-only disease.
- Prior treatment requirements: In general, participants eligible for the BCGunresponsive and BCG-exposed cohorts of the study should have demonstrated persistent or recurrent disease after receiving at least 5 out of 6 doses of the BCG induction therapy. Participants eligible for BCG-naive cohorts in Part 3 and BCGnaive backfill cohorts in Part 2 should have not received prior intravesical BCG. Participants may be further categorized based on the following criteria: 1) BCG-unresponsive participants: with persistent or recurrent CIS within 12 months of completion of adequate BCG therapy, which is defined as one of the following: at least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy; or at least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses of a second induction course; Recurrent highgrade Ta/T1 disease within 6 months of completion of adequate BCG therapy; T1 high-grade disease at the first evaluation following an induction BCG course. 2) BCG-exposed participants: with high-grade persistent or recurrent NMIBC within 24 months of the last BCG dose, who have received at least 5 out of 6 doses of the BCG induction therapy and do not meet the definition of BCGunresponsive. This includes those who declined additional BCG treatment, BCG is not available, or cannot tolerate additional BCG in the opinion of the investigator; 3) BCG-naïve: Patients who have never received intravesical BCG therapy, who declined standard of care BCG treatment, or BCG is not available; Patients with high-risk recurrence >24 months after their last dose of BCG may be treated as BCG-naive patients; Other BCG-treated participants, specifically those who have demonstrated persistent or recurrent disease after receiving at least 5 of 6 doses of the induction therapy, with or without maintenance, and do not meet the criteria of BCGunresponsive or BCG-exposed, may be eligible. Additionally, participants who have demonstrated persistent or recurrent disease on other institutional standard BCG alternative options (eg, gemcitabine/docetaxel, mitomycin, recombinant BCG) may be eligible. Note: Prior treatment requirements for specific cohorts or slots may vary, depending on the study parts, cohorts, and open slots. For a given cohort or slot, please check with the sponsor clinician or delegate for confirmation before consenting the patient. Prior intravesical chemotherapy for NMIBC is allowed in all cohorts.
- Have refused or are ineligible or not appropriate for radical cystectomy.
- Tissue Requirement: Prior to enrollment, confirmation of availability of the tumor tissue obtained within the last 6 months from the most recent TURBT for submission to the central laboratory. If a second TURBT was performed, the tumor tissue from the TURBT procedure that supports the primary diagnosis for study eligibility should be the tumor tissue used for submission. On-treatment tumor biopsy is optional but encouraged, unless mandated by sponsor based on emerging data, or participating in the Biomarker Cohort/Subsets, or for disease assessment as detailed in Section 8.2.
- ECOG PS 0 or 1.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
Critères d'exclusion :
- 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.
- Serum or urine pregnancy test (for females of childbearing potential) positive at screening.
- Renal impairment as defined by an eCrCl of <45 mL/min as calculated using the CKD-EPI creatinine equation, adjusted for body surface area (see Section 10.7). In equivocal cases, a 24-hour urine collection test may be used to estimate the CrCl more accurately. Participants with an eCrCl of 30-45 mL/min may be allowed based on emerging data.
- Known or suspected hypersensitivity to antibodies or infused therapeutic proteins, or known previous allergies or adverse reactions to BCG (applicable only if receiving BCG).
- Hepatic dysfunction defined as: Total bilirubin ≥1.5 x ULN (≥3 x ULN in case of documented Gilbert’s syndrome); AST and ALT ≥2.5 x ULN; Alkaline phosphatase ≥2.5 x ULN.
- Evidence of muscle-invasive, locally advanced or metastatic urothelial carcinoma or concurrent extravesical, non-muscle invasive urothelial carcinoma. Patients who have been treated with TMT for MIBC and subsequently develop NMIBC should be excluded.
- Any concurrent febrile illness, urinary tract infection, or gross hematuria/traumatic catheterization, or bladder perforation. Study drug treatment should be postponed until the resolution of these conditions. A period of at least 7-14 days should pass before the planned first dose of study intervention (C1D1) following bladder or prostatic surgery, including biopsy, transurethral resection, or traumatic catheterization. For urinary tract infections, study treatment can be started 7-14 days after the resolution of symptoms. Participants with large post-void residual urine (PVR) (e.g., >300 mL, measured according to institutional standards) may be excluded based on emerging data.
- Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, Bowen's disease, prostate intraepithelial neoplasm and ≤6 Gleason grade prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation or castration). Patients can have a history of noninvasive UTUC, have undergone treatment, and have no evidence of disease for at least 2 years to be eligible for inclusion. Participants with a history of other curatively treated cancers must be reviewed by the sponsor prior to entering the study.
- History of Grade ≥3 immune mediated AE (including AST/ALT elevations that were considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (e.g., immune checkpoint inhibitors) and required immunosuppressive therapy. This criterion is specific to combinations with sasanlimab.
- Active or prior autoimmune disease or irAE that might deteriorate when receiving an immunostimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, alopecia, hypothyroid or hyperthyroid disease not requiring immunosuppressive treatment are eligible. Well-controlled endocrinopathy with replacement hormone is permissible. This criterion is specific to combinations with sasanlimab.
- Major surgery within 2 weeks prior to Day 1.
- Known ongoing medical history of inflammatory bowel disease, noninfectious pneumonitis / interstitial lung disease, or pulmonary fibrosis.
- Prior solid organ transplantation or allogenic stem-cell transplantation.
- Hematologic abnormalities defined as: ANC <1000/mm3 or 1.00 x 109/L; Platelets <100,000/mm3 or 100 x109/L; Hemoglobin <10 g/dL. Appropriate treatment with supplemental iron (oral [PO] or intravenous [IV]) is required for iron deficiency anemia.
- Participants with active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, known HIV or AIDS-related illness, and TB infection.
- Impaired cardiovascular function or clinically significant cardiovascular disease, as follows: 1) Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (e.g., baseline QTcF >470 ms, complete LBBB, signs of an acute or indeterminate age- myocardial infarction, ST-T interval changes suggestive of active myocardial ischemia, second or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF >470 ms, or QRS complex exceeds 120 ms, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS complex values should be used to determine the participant’s eligibility. Computer interpreted-ECGs should be over-read by a physician experienced in reading ECGs before excluding participants. Cases must be discussed in detail with the sponsor to judge eligibility. 2) Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, clinically important atrial or ventricular arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), serious conduction system abnormalities (e.g., bifascicular block [defined as right bundle branch and left anterior or posterior hemiblock], 3rd degree AV block), unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thrombo-embolic disease. 3) Ongoing cardiac dysrhythmias of NCI CTCAE ≥ Grade 2. If a participant has a cardiac rhythm device/pacemaker placed and QTcF >470 ms, the participant may be eligible. Participants with cardiac rhythm device/pacemaker must be discussed with the sponsor to judge eligibility. Patients with non-symptomatic, well-controlled atrial fibrillation who have had no change in medication for the past six months are eligible.
- 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.
- Concomitant anti-cancer therapy for NMIBC is not allowed.
- Participants who received any systemic or intravesical chemotherapy or immunotherapy from the time of most recent positive TURBT to the planned first dose of study intervention (Day 1). Note, single dose intravesical chemotherapy as part of the most recent positive TURBT according to the current locally applicable guidelines is allowed.
- Vaccination with live or live-attenuated vaccines within 4 weeks prior to start of treatment.
- Prior radiation therapy to the bladder.
- Current use of any prohibited concomitant medications. This includes, but is not limited to, antibiotics deemed by the investigator to potentially interfere with the effectiveness of BCG (applicable only if receiving BCG). See Section 6.9
- Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of start of treatment. Inhaled, topical, intraocular, intranasal, and intraarticular steroids are permitted in the absence of active immune disease. Adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Previous administration with 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 their participation in this study. A participant may be eligible even if they are in the follow-up phase of an investigational study as long as they have not received treatment in that study for at least 1 month and there are no additional sample collections required for the other study.
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