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)

Phase 1

Recruiting

• Conditions: Non-muscle Invasive Bladder Cancer
• Interventions: Drug: Eciskafusp Alfa; Drug: BCG Medac Strain

• Registration Number: NCT06816017
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-04
• Study First Submitted QC: 2025-02-04
• Study First Posted: 2025-02-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-22
• Last Update Posted: 2025-05-23
• Study Start: 2025-06-15
• Primary Completion: 2028-10-31
• Study Completion: 2030-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase I: Dose Escalation	BCG Medac Strain	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.
Phase II: Dose Extension (Cohort A)	Eciskafusp Alfa	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.
Phase II: Dose Extension (Cohort A)	BCG Medac Strain	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.
Phase II: Dose Extension (Cohort B)	Eciskafusp Alfa	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.
Phase I: Dose Escalation	Eciskafusp Alfa	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.

Primary Outcome Measures

Name	Time	Method
Phase I: Recommended Dose for Extension (RDE) of Eciskafusp Alfa in Combination With BCG	At Month 25
Phase I: Number of Participants With Adverse Events (AEs)	From Baseline (Day 1) up to 28 days after final dose of study treatment (up to Month 26)
Phase II (Cohort A): Complete Response Rate (CRR) at 12 Months	At Month 12
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	From Day 1 up to Day 14

Secondary Outcome Measures

Name	Time	Method
Phase I and Phase II: CRR at 6, 18 and 24 Months	At Months 6, 18 and 24
Phase I and Phase II (Cohort B): CRR at 12 Months	At Month 12
Phase I and Phase II: Time to Worsening of NMIBC Grade or Stage, or Death	Time from the first dose of study treatment to the first occurrence of documented worsening of grade, stage or death from any cause, whichever occurs first (up to Month 36)
Phase I and Phase II: DOR Rate at Specific Timepoints	At Months 6, 12, 18, 24, 30 and 36
Phase II: Baseline Urine Tumor Deoxyribonucleic Acid (DNA)	Baseline (Day 1 predose)
Phase I and Phase II: CRR at any Time	Up to Month 36
Phase I and Phase II: Duration of Response (DOR)	Time from the first occurrence of a documented CR until the time of evidence that the participant no longer meets the definition for CR or death from any cause, whichever occurs first (up to Month 36)
Phase II: Number of Participants With AEs	From Baseline (Day 1) up to 28 days after final dose of study treatment (up to Month 26)
Phase I and Phase II: Progression Free Survival (PFS) to Muscle Invasive or Metastatic Disease or Death	Time from the first dose of study treatment to the first occurrence of documented muscle-invasive or metastatic disease or death from any cause, whichever occurs first (up to Month 36)
Phase II: Number of Participants With Cluster of Differentiation 8+ (CD8+) T cell in TME	Predose (-12 weeks to -14 days or archival)
Phase I and II: Time to Cystectomy	Time from the first dose of study treatment to the first occurrence of documented cystectomy or death from any cause, whichever occurs first (up to Month 36)
Phase I and Phase II: Number of Participants With Anti-drug Antibodies (ADAs) to Eciskafusp Alfa	Up to Month 36
Phase II: Programmed Cell Death Ligand 1 (PD-L1) Expression in the Tumor Microenvironment (TME) Pre-treatment and During the Study	Predose (-12 weeks to -14 days or archival) and Postdose at Month 6	PD-L1 expression may be assessed at other timepoints when on-treatment biopsies will be collected.
Phase II: Amount of Urine Tumor DNA at Baseline and During the Study	Up to Month 25

Trial Locations

Locations (9)

A.O.U di Verona Policlinico G.B. Rossi; 🇮🇹 Verona, Veneto, Italy

Hospital Umum Sarawak; 🇲🇾 Kuching, Sarawak, Malaysia

Macquarie University Hospital; 🇦🇺 Macquarie Park, New South Wales, Australia

NKI/AvL; 🇳🇱 Amsterdam, Netherlands

UMC St Radboud; 🇳🇱 Nijmegen, Netherlands

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gda?sk, Poland

AIDPORT Sp. z o. o.; 🇵🇱 Skórzewo, Poland

Hospital Univ. 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario Virgen de la Victoria; 🇪🇸 Malaga, Spain