Non-muscle Invasive Bladder Cancer
Conditions
Keywords
BCG-unresponsive Non-muscle Invasive Bladder Cancer
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.
Interventions
DRUGEciskafusp Alfa
Participants will receive eciskafusp alfa via intravesical instillation.
DRUGBCG Medac Strain
Participants will receive BCG via intravesical instillation.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: CRR at any Time | 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: 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 | — |
| Phase I and Phase II: Number of Participants With Anti-drug Antibodies (ADAs) to Eciskafusp Alfa | 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) | — |
Countries
Australia, Italy, Malaysia, Netherlands, Poland, Spain
Outcome results
None listed