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.

Study Overview

• Status: Withdrawn
• Conditions: Non-muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: Eciskafusp Alfa; Drug: BCG Medac Strain

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2113
      • Macquarie University Hospital
• Italy
  • Veneto
    • Verona, Veneto, Italy, 37134
      • A.O.U di Verona Policlinico G.B. Rossi
• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Hospital Umum Sarawak
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • NKI/AvL
  • Nijmegen, Netherlands, 6525 GA
    • UMC St Radboud
• Poland
  • Gda?sk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Skórzewo, Poland, 60-185
    • AIDPORT Sp. z o. o.
• Spain
  • Madrid, Spain, 28041
    • Hospital Univ. 12 de Octubre
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: Dose Escalation; 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.	Drug: Eciskafusp Alfa; Participants will receive eciskafusp alfa via intravesical instillation.; Other Names: RO7284755; Drug: BCG Medac Strain; Participants will receive BCG via intravesical instillation.
Experimental: Phase II: Dose Extension (Cohort A); 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.	Drug: Eciskafusp Alfa; Participants will receive eciskafusp alfa via intravesical instillation.; Other Names: RO7284755; Drug: BCG Medac Strain; Participants will receive BCG via intravesical instillation.
Experimental: Phase II: Dose Extension (Cohort B); 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.	Drug: Eciskafusp Alfa; Participants will receive eciskafusp alfa via intravesical instillation.; Other Names: RO7284755

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 I: Number of Participants With Dose Limiting Toxicities (DLTs)	From Day 1 up to Day 14
Phase I: Recommended Dose for Extension (RDE) of Eciskafusp Alfa in Combination With BCG	At Month 25
Phase II (Cohort A): Complete Response Rate (CRR) at 12 Months	At Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I and Phase II: CRR at any Time		Up to Month 36
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: 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 I and Phase II: DOR Rate at Specific Timepoints		At Months 6, 12, 18, 24, 30 and 36
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: 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 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 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: 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	PD-L1 expression may be assessed at other timepoints when on-treatment biopsies will be collected.	Predose (-12 weeks to -14 days or archival) and Postdose at Month 6
Phase II: Number of Participants With Cluster of Differentiation 8+ (CD8+) T cell in TME		Predose (-12 weeks to -14 days or archival)
Phase II: Baseline Urine Tumor Deoxyribonucleic Acid (DNA)		Baseline (Day 1 predose)
Phase II: Amount of Urine Tumor DNA at Baseline and During the Study		Up to Month 25

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2025
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2030

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Actual): June 16, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: BCG-unresponsive Non-muscle Invasive Bladder Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms
• Other Study ID Numbers: BP45381; 2024-515410-41-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No