A Study of Eciskafusp Alfa and Bacillus Calmette-Guérin (BCG) in Participants with High-Risk Bladder Cancer Unresponsive to BCG Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Apr 2025 → 17 May 2025

Decision date (initial)

2025-03-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Others, Pharmacokinetic

Phase I: To evaluate the safety and tolerability of eciskafusp alfa in combination with Bacillus Calmette-Guérin (BCG). Phase I: To determine the maximum-tolerated dose (MTD) and/or the recommended dose for extension (RDE) of eciskafusp alfa in combination with BCG. Phase II (Cohort A): To evaluate the anti-tumor activity of study treatment by evaluating the absence of high-risk non-muscle invasive bladder cancer (NMIBC) or progressive disease, as determined by cystoscopy, and radiologic imaging and retrospective central pathology review of cytology and biopsy

Secondary objectives 5

1. Phase I, and Phase II (Cohorts A and B): To evaluate the anti-tumor activity of study treatment by evaluating the absence of high-risk NMIBC or progressive disease, as determined by cystoscopy, and radiologic imaging, and pathology review (local in Phase I, and retrospective central in Phase II) of cytology and biopsy
2. Phase II (Cohorts A and B): To evaluate the safety and tolerability of study treatment
3. Phase I and Phase II (Cohorts A and B): To evaluate the immune response against eciskafusp alfa intravesically during and after study treatment
4. Phase II: To determine the association of baseline characteristics in the tumor microenvironment (TME) and urine with clinical outcome
5. Phase II: To determine the pharmacodynamic effects of eciskafusp alfa in urine

Conditions and MedDRA coding

BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Type of Participants and Disease Characteristics: Pathologically confirmed high risk non muscle invasive transitional cell carcinoma classified according to World Health Organization (WHO) grading system. Only participants with carcinoma in situ (CIS) (with or without Ta/T1 disease) are eligible. Patients with tumors of mixed histology are allowed, but transitional cell carcinoma must be the predominant histology. Participants must have CIS present on the tumor sample from the most recent transurethral resection of bladder tumor (TURBT)
2. General conditions: Parameter: Eastern Cooperative Oncology Group (ECOG) performance status Criteria applicable to Phase I: 0 or 1 Criteria applicable to Phase II (Cohorts A and B): 0, 1, or 2
3. Type of Participants and Disease Characteristics: Absence of resectable disease after TURBT procedures (residual CIS acceptable; participants with T1 tumors must undergo repeat resection and biopsy [inclusive of muscularis propria] of the T1 tumor site if initial biopsy did not include muscularis propria).
4. Type of Participants and Disease Characteristics: Presence of BCG-unresponsive disease defined as persistent or recurrent CIS (± recurrent Ta/T1 disease) within 12 months of receiving adequate BCG therapy (defined as at least 5 of 6 doses of an initial induction course plus either at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course)
5. Type of Participants and Disease Characteristics: The participant is considered ineligible for radical cystectomy or has elected not to undergo the procedure. Reasons for ineligibility or refusal of radical cystectomy should be discussed with the participant as part of the informed consent process and should be captured on the appropriate electronic case report form (eCRF)

Exclusion criteria 6

1. Prior treatment with IL-2/IL-15
2. History of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer (inclusive of ureter, urethra, or renal pelvis)
3. Medical Conditions: Known HIV infection (no testing required at screening)
4. Medical Conditions: History of radiotherapy of the bladder
5. Medical Conditions: History of perforation of the bladder
6. Known hypersensitivity to BCG

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Phase I: Incidence, nature, and severity of adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
2. Phase I: Nature and frequency of dose-limiting toxicities (DLTs)
3. Phase I: RDE to be selected based on evaluation of safety
4. Phase II (Cohort A): Complete response (CR) rate at 12 months

Secondary endpoints 14

1. Phase I, and Phase II (Cohorts A and B): CR rate at any time
2. Phase I, and Phase II (Cohorts A and B): CR rate at 6, 18, and 24 months
3. For Phase I, and Cohort B in Phase II: CR rate at 12 months
4. Phase I, and Phase II (Cohorts A and B): Duration of response (DoR)
5. Phase I, and Phase II (Cohorts A and B): DoR rate at specific time points (at 6, 12, 18, 24, 30, and 36 months).
6. Phase I, and Phase II (Cohorts A and B): Time to worsening of grade or stage, or death.
7. Phase I, and Phase II (Cohorts A and B): Progression free survival (PFS) to muscle invasive or metastatic disease or death.
8. Phase I, and Phase II (Cohorts A and B): Time to cystectomy.
9. Phase II (Cohorts A and B): Incidence, nature, and severity of adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
10. Phase II (Cohorts A and B): Incidence and titer of eciskafusp alfa anti-drug antibodies (ADAs) during the study relative to prevalence of ADAs at baseline (serum).
11. Phase II: Pre-treatment and on-treatment (as available) PD-L1 expression in the TME.
12. Phase II: Pre-treatment CD8+ T cell prevalence.
13. Phase II: Baseline urine tumor DNA
14. Phase II: On treatment vs. baseline urine tumor DNA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 5

Locations

7 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications