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)

NCT06816017 | Withdrawn Phase 1

• 2 other identifiers: BP453812024-515410-41-00
• Study Type: interventional
• Target: N/A
• Locations: 6 countries
• Sites: 9

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.

Conditions

Non-muscle Invasive Bladder Cancer

Keywords

BCG-unresponsive Non-muscle Invasive Bladder Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (14)

• 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

Study Arms (3)

Phase I: Dose Escalation

EXPERIMENTAL

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; Drug: BCG Medac Strain

Phase II: Dose Extension (Cohort A)

EXPERIMENTAL

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; Drug: BCG Medac Strain

Phase II: Dose Extension (Cohort B)

EXPERIMENTAL

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

Interventions

Eciskafusp Alfa DRUG

Participants will receive eciskafusp alfa via intravesical instillation.

Also known as: RO7284755

Phase I: Dose Escalation; Phase II: Dose Extension (Cohort A); Phase II: Dose Extension (Cohort B)

BCG Medac Strain DRUG

Participants will receive BCG via intravesical instillation.

Phase I: Dose Escalation; Phase II: Dose Extension (Cohort A)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

Macquarie University Hospital

Macquarie Park, New South Wales, 2113, Australia

Location

A.O.U di Verona Policlinico G.B. Rossi

Verona, Veneto, 37134, Italy

Location

Hospital Umum Sarawak

Kuching, Sarawak, 93586, Malaysia

Location

NKI/AvL

Amsterdam, 1066 CX, Netherlands

Location

UMC St Radboud

Nijmegen, 6525 GA, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

Location

AIDPORT Sp. z o. o.

Skórzewo, 60-185, Poland

Location

Hospital Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2025
• First Posted: February 10, 2025
• Study Start: June 15, 2025
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2030
• Last Updated: June 16, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

IT (1); NL (2); PL (2); AU (1); ES (2); MY (1)