A Study to Evaluate Eciskafusp Alfa in Combination With Bacillus Calmette-guerin (BCG) in Participants With BCG-unresponsive High-risk Non-muscle Invasive Bladder Cancer (NMIBC)

A Phase I/II, Open-label, Dose Escalation and Extension Study of Intravesical Eciskafusp Alfa in Combination With Bacillus Calmette-guerin (BCG) in Participants With BCG-unresponsive High-risk Non-muscle Invasive Bladder Cancer (NMIBC)

The study aims to establish the safety, tolerability, pharmacokinetics (PK), relevant biomarkers, pharmacodynamics (PD) and preliminary anti-tumor activity of the intravesical administration of eciskafusp alfa in combination with BCG in participants with BCG-unresponsive high-risk NMIBC.

The study plans a similar evaluation of eciskafusp alfa in monotherapy following a positive interim analysis of the combination therapy.

Inclusion Criteria:

• Pathologically confirmed high risk non muscle invasive transitional cell carcinoma classified according to World Health Organization (WHO) grading system
• Absence of resectable disease after transurethral resection of bladder tumor (TURBT) procedures
• The most recent cystoscopy/TURBT must have been performed within 12 weeks and up to 14 days of the first dose of study treatment
• Presence of BCG-unresponsive disease defined as persistent or recurrent carcinoma in situ [CIS] (± recurrent Ta/T1 disease) within 12 months of receiving adequate BCG therapy
• The participant is considered ineligible for radical cystectomy or has elected not to undergo the procedure.
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Positive hepatitis B surface antibody (HBsAb) test at screening
• Negative hepatitis C virus (HCV) antibody test at screening

Exclusion Criteria:

• Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders
• Active infections (both systemic and local urinary)
• Congenital or acquired immune deficiencies resulting in immunosuppression
• Known human immunodeficiency virus (HIV) infection
• History of radiotherapy of the bladder
• History of perforation of the bladder
• Major surgery or significant traumatic injury within 28 days prior to first administration of study treatment or anticipation of the need for major surgery during treatment
• Participants currently receiving investigational or commercial anti-cancer agents or anti-cancer therapies other than BCG, and supportive care therapies for active disease
• Any intervening intravesical immunotherapy or chemotherapy from the time of the most recent cytoscopy/TURBT to the start of study treatment
• Systemic immune-modulating and systemic immunosuppressive agents/medication
• Administration of a live, attenuated vaccine within 28 days prior to first administration of study treatment
• Recurrence of BCG unresponsive CIS > 12 months after last BCG instillation
• Concurrent second malignancy