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)

Roche

Status and phase: Enrolling; Phase 1

Conditions: Non-muscle Invasive Bladder Cancer

Treatments: Drug: BCG Medac Strain; Drug: Eciskafusp Alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT06816017

2024-515410-41-00 (Other Identifier)

BP45381

Details and patient eligibility

About

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.

Enrollment: 110 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

110 participants in 3 patient groups

Phase I: Dose Escalation

Experimental group

Description:

Participants will receive multiple ascending doses of eciskafusp alfa in combination with a fixed dose of BCG administered as an intravesicular instillation up to a maximum of 25 months or until detection of high-risk disease or disease progression, toxicity, or withdrawal from study treatment for other reasons, whichever occurs first.

Treatment:

Drug: Eciskafusp Alfa

Drug: BCG Medac Strain

Phase II: Dose Extension (Cohort A)

Experimental group

Description:

Participants will receive eciskafusp alfa at the maximum tolerated dose (MTD) and/or the recommended dose for extension (RDE), as determined in Phase 1, in combination with a fixed dose of BCG administered as an intravesical instillation up to a maximum of 25 months or until detection of high-risk disease or disease progression, toxicity, or withdrawal from study treatment for other reasons, whichever occurs first.

Treatment:

Drug: Eciskafusp Alfa

Drug: BCG Medac Strain

Phase II: Dose Extension (Cohort B)

Experimental group

Description:

Participants will receive eciskafusp alfa as monotherapy at the MTD or RDE determined in Phase 1, administered as an intravesical instillation up to a maximum of 25 months or until detection of high-risk disease or disease progression, toxicity, or withdrawal from study treatment for other reasons, whichever occurs first.

Treatment:

Drug: Eciskafusp Alfa