Clinical trial NCT06816017: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Non-muscle Invasive Bladder Cancer
Keywords: BCG-unresponsive Non-muscle Invasive Bladder Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2025-02-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase I: Number of Participants With Adverse Events (AEs)
timeFrame: From Baseline (Day 1) up to 28 days after final dose of study treatment (up to Month 26)
measure: Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From Day 1 up to Day 14
measure: Phase I: Recommended Dose for Extension (RDE) of Eciskafusp Alfa in Combination With BCG
timeFrame: At Month 25
measure: Phase II (Cohort A): Complete Response Rate (CRR) at 12 Months
timeFrame: At Month 12
Secondary outcomes:
measure: Phase I and Phase II: CRR at any Time
timeFrame: Up to Month 36
measure: Phase I and Phase II: CRR at 6, 18 and 24 Months
timeFrame: At Months 6, 18 and 24
measure: Phase I and Phase II (Cohort B): CRR at 12 Months
timeFrame: At Month 12
measure: Phase I and Phase II: Duration of Response (DOR)
timeFrame: 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)
measure: Phase I and Phase II: DOR Rate at Specific Timepoints
timeFrame: At Months 6, 12, 18, 24, 30 and 36
measure: Phase I and Phase II: Time to Worsening of NMIBC Grade or Stage, or Death
timeFrame: 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)
measure: Phase I and Phase II: Progression Free Survival (PFS) to Muscle Invasive or Metastatic Disease or Death
timeFrame: 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)
measure: Phase I and II: Time to Cystectomy
timeFrame: 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)
measure: Phase II: Number of Participants With AEs
timeFrame: From Baseline (Day 1) up to 28 days after final dose of study treatment (up to Month 26)
measure: Phase I and Phase II: Number of Participants With Anti-drug Antibodies (ADAs) to Eciskafusp Alfa
timeFrame: Up to Month 36
measure: Phase II: Programmed Cell Death Ligand 1 (PD-L1) Expression in the Tumor Microenvironment (TME) Pre-treatment and During the Study
timeFrame: Predose (-12 weeks to -14 days or archival) and Postdose at Month 6
measure: Phase II: Number of Participants With Cluster of Differentiation 8+ (CD8+) T cell in TME
timeFrame: Predose (-12 weeks to -14 days or archival)
measure: Phase II: Baseline Urine Tumor Deoxyribonucleic Acid (DNA)
timeFrame: Baseline (Day 1 predose)
measure: Phase II: Amount of Urine Tumor DNA at Baseline and During the Study
timeFrame: Up to Month 25
Other outcomes:
Locations:
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Verona
country: Italy
facility: A.O.U di Verona Policlinico G.B. Rossi
state: Veneto
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
state: Sarawak
city: Amsterdam
country: Netherlands
facility: NKI/AvL
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Skórzewo
country: Poland
facility: AIDPORT Sp. z o. o.
city: Madrid
country: Spain
facility: Hospital Univ. 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: