A study investigating whether it is possible to preserve the bladder in participants with bladder cancer by starting with the drugs enfortumab vedotin plus pembrolizumab, followed by further treatment of the bladder depending on the effect on the bladder tumor: FIDELIO

Korábbi kezelés

• Previous pelvic irradiation
• Severe infections within 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Active infec-tion requiring systemic therapy is excluded as well.
• Has not adequately recovered from major surgery or has ongoing surgical complications.
• Major pelvic surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for the disease under study.
• Has had an allogenic tissue/solid organ transplant.
• Previous intravenous systemic therapy for bladder cancer, including chemotherapy, check-point inhibition or antibody-drug conjugate.
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

Más betegség

• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Exceptions: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ that have undergone potentially curative therapy are not ex-cluded. Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eli-gible.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, EV and/or any of its excipients in drug formulations (including histidine, trehalose dihydrate, and polysorbate 20).
• Has active autoimmune disease that has required systemic treatment in the past 2 years. Ex-ceptions that can still be included: -Endocrine disease with replacement therapy (e.g., thyroxine, insulin, or physiologic cortico-steroid) -Patients with vitiligo, psoriasis or other mild skin disease -Gout is not considered an auto-immune disease. Patients should not have had an episode of active arthritis within 30 days of start of therapy.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are al-lowed if the disorder is being adequately treated in the opinion of the investigator.
• Upper tract urothelial cancer
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Laborértékek

• A history of uncontrolled diabetes. Uncontrolled diabetes is defined as HbA1c ≥8% or HbA1c 7% to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
• Known active Human Immunodeficiency Virus infection, or tuberculosis, or other active infec-tion: - HIV-positive patients are eligible if the following applies:  Receives antiretroviral therapy (ART), without changes in drugs or dose modification, for at least 4 weeks prior to treatment and continued while enrolled on study.  CD4+ T-cell count ≥350 cells/mm3 at the time of screening  Participants on ART must have achieved and maintained virologic suppres-sion defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening  No AIDS defining opportunistic infection within the past 12 months, or a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease. - In patients with a known history of hepatitis B infection, Hepatitis B surface antigen should be negative at time of screening. Patients having chronic hepatitis B are not eligible. - Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s abil-ity to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Egyéb

• Ongoing sensory or motor neuropathy Grade 2 or higher.
• Extensive carcinoma in situ (CIS) of the bladder
• Bilateral hydronephrosis
• Contra-indication to one of the study treatment components

• Participants who are at least 18 years of age on the day of signing informed consent.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Patients with histologically confirmed cT2-4aN0-1M0 urothelial bladder cancer, seeking an al-ternative to radical cystectomy and/or patients who are medically unfit for surgery. Variant histology allowed, exceptions: • no pure (>90%) squamous • no >50% adenocarcinoma • no >50% sarcomatoid component • no >10% plasmacytoid component • no small cell component
• Archival tumor tissue sample or newly obtained TURB of the bladder tumor is available. For-malin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Have adequate organ function as defined in Table 3of the protocol. Specimens must be collected within 14 days prior to the start of study intervention.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Not of childbearing potential (see section 9.2.1) OR • Of childbearing potential and: - Uses a contraceptive method that is highly effective. - Has a negative urine or serum pregnancy test within 72 hours before the first dose of study intervention. Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention (for pembrolizumab) or 180 days (EV) after the last dose of study intervention. A male participant agrees to the following during the intervention period and for at least 180 days after the last dose of EV: Refrains from donating sperm plus either: -Abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent -Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to med-ical cause) as detailed in section 9.2.1. of the protocol