Pembrolizumab i kombinasjon med BCG

Cohort A: BCG with or without pembrolizumab for HR NMIBC Key Eligibility Requirements*: • Histologic diagnosis of UC, staging consistent with high risk non-muscle invasive bladder cancer (T1, high grade Ta and/or CIS) confirmed by central lab • Treatment with 1 adequate course of BCG induction therapy for the treatment of HR NMIBC defined as at least 5 intravesical instillations of BCG within a 10 week period of time • Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC defined as: • HR NMIBC: recurrent T1, high grade Ta and/or CIS • Persistent: remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction (Note: persistent T1 not eligible for study), or • Recurrent: reappearance of HR NMIBC after achieving a CR or tumor-free state within 6 months (+ 4 weeks) after start of BCG induction. The recurrence must be within 24 months of last exposure to BCG [with up to an additional 56 days allowed to account for delays in the 24 month assessment] • ECOG performance status of 0, 1 or 2 Cohort B: A Phase 3 trial of BCG with or without pembrolizumab for BCG Naïve HR NMIBC Key Eligibility Requirements*: • Histologic diagnosis of UC, staging consistent with high risk non-muscle invasive bladder cancer (T1, high grade Ta and/or CIS) confirmed by central lab • Has NOT received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry • Has undergone cystoscopy/TURBT to remove all resectable disease within 12 weeks prior to randomization. Participants with recurrent T1 disease should have undergone a restaging TURBT procedure between 14 to 56 days prior to randomization to confirm complete resection and that the participant continues to meet eligibility criteria • Have provided tissue for biomarker analysis from the most recent TURBT/biopsy procedures from which tumor sample is available • ECOG performance status of 0, 1 or 2 *Please note there are additional eligibility requirements Exclusion Criteria: • Has persistent T1 disease following an induction course of BCG • Has muscle invasive (i.e., T2, T3, T4), locally advanced non-resectable or metastatic UC • Has concurrent extra-vesical (i.e., urethra, ureter, renal pelvis) non-muscle invasive TCC of the urothelium, concurrent upper tract involvement, or invasive prostatic TCC including T1 or greater disease, or ductal invasion • WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization • Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment • Has a known additional malignancy that is progressing or requires active treatment within the past 3 years • Has an active autoimmune disease that has required systemic treatment in past 2 years • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis • Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG • Has an active infection requiring systemic therapy • Has a known history of human immunodeficiency virus (HIV) infection • Has a known history of Hepatitis B or known active Hepatitis C virus infection • Has evidence of active tuberculosis • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment