A study to learn about nadofaragene firadenovec given alone or together with gemcitabine and docetaxel or, pembrolizumab in adults with non-muscle invasive bladder cancer and no response to treatment with Bacillus Calmette-Guerin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ferring Pharmaceuticals A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

29 Sep 2025 → ongoing

Decision date (initial)

2025-09-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512177-27-01

WHO UTN

U1111-1299-0176

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of intravesical instillation, including reinduction, of nadofaragene firadenovec alone or in combination with chemotherapy (gemcitabine and docetaxel) or immunotherapy (pembrolizumab) in subjects with high-grade Bacillus Calmette-Guerin (BCG) unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without concomitant high-grade Ta or T1 papillary disease

Conditions and MedDRA coding

High-risk Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ(CIS) with or without papillary tumours

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Signed informed consent obtained before beginning any trial-related procedures
2. Diagnosed, as documented, with carcinoma in situ (CIS) ±Ta/T1 high-grade disease • For T1 disease biopsies should contain muscle fibres
3. Unresponsive to ≥2 courses of Bacillus Calmette-Guerin (BCG) therapy within the last 12 months. BCG-unresponsive refers to subjects with high-grade non-muscle-invasive bladder cancer (NMIBC) who are unlikely to benefit from and who will not be receiving further intravesical BCG. The term “BCG-unresponsive” includes subjects who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response (CR) to BCG, relapse with CIS within 12 months of their last intravesical treatment with BCG or relapse with high grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria define the subjects who may be included in the trial: • Have received at least 2 courses of BCG within a 12-month period – defined as at least 5 of 6 induction BCG instillations and at least 2 of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG is not given. o Exception: those who have T1 high-grade disease at 1st evaluation after induction BCG alone (at least 5 of 6 doses) may qualify in the absence of disease progression • At the time of tumour recurrence, subjects with CIS alone or high-grade Ta/T1 with CIS should be within 12 months of last exposure to BCG • No maximum limit to the amount of BCG administered • All visible papillary tumours must be resected and those with persistent T1 disease on transurethral resection of bladder tumour (TURBT) should undergo an additional re TURBT within 14 to 70 days prior to beginning trial treatment. Obvious areas of CIS should also be fulgurated
4. Eastern Cooperative Oncology Group (ECOG) status ≤2
5. Aged ≥18 years at the time of consent
6. Available for the whole duration of the trial
7. Life expectancy >2 years, in the opinion of the investigator
8. Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumour by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or magnetic resonance imaging (MRI) with or without urogram performed within 6 months of enrolment. Absence of locally advanced disease as assessed by CT scan or MRI
9. Subjects who elect not to undergo cystectomy
10. Subjects with prostate cancer on active surveillance at low risk for progression are permitted to be included into the trial at the discretion of the investigator (see exclusion criterion 16)
11. Females of reproductive potential must have a negative highly sensitive urine or serum pregnancy test upon entry into this trial and be willing to use highly effective contraception during treatment with the investigational medicinal product (IMP) and for 6 months following the last dose. Otherwise, female subjects must be post-menopausal (no menstrual period for a minimum of 12 months, as confirmed by follicle-stimulating hormone levels) or surgically sterile. • Highly effective methods of contraception include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, and sexual abstinence.
12. Male subjects must use highly effective contraception and a condom during sexual contact regardless of partner’s childbearing potential, until 3 months following the last trial drug administration. Effective contraception is specified in inclusion criterion 11.
13. Adequate laboratory values: • Haemoglobin ≥10 g/dL • White blood cells (WBC) ≥3800/µL • Absolute neutrophil count (ANC) ≥2000/µL • Platelet count ≥100,000/µL • International normalised ratio (INR)a below institutional upper limit of normal (ULN) • Activated partial thromboplastin time (aPTT)a below institutional ULN • Aspartate aminotransferase (AST) ≤1.5 x ULN • Alanine aminotransferase (ALT) ≤1.5 x ULN • Total bilirubin ≤1.5 x ULN • Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 a It is accepted that subjects receiving anticoagulation therapy would not have INR and aPTT results that fall within ‘normal limits’. It is not intended to exclude these subjects and therefore medical discretion is permitted for subjects who have clinically acceptable results in regard to their current concomitant anticoagulant therapy.

Exclusion criteria 19

1. Current or previous evidence of muscle-invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples of increased risk of muscle-invasive disease include but are not limited to: • Presence of lymphovascular invasion and / or micropapillary, sarcomatoid, plasmacytoid and / or neuroendocrine disease as shown in the histology of the biopsy sample • Subjects with CIS+T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumour
2. Current systemic therapy for bladder cancer other than IMP used in randomisation arm
3. Current or prior investigational treatment for BCG-unresponsive NMIBC or any other investigational drug (drug used in a clinical trial, i.e. drug used in a Ferring sponsored non-interventional study does not apply) within 1 month prior to screening
4. Current or prior pelvic external beam radiotherapy within 2 years of screening
5. Prior treatment with nadofaragene firadenovec at any time
6. Prior systemic therapy for bladder cancer at any time
7. Prior intravesical chemotherapy for the treatment of BCG-unresponsive NMIBC (see exclusion criterion 19)
8. Use of other adenovirus vector-based drugs, e.g. COVID-19 vaccines, within 14 days before and after nadofaragene firadenovec instillation
9. Suspected hypersensitivity or immune-mediated reactions to any of the IMPs
10. Current or prior autoimmune disease
11. Immunocompromised, or immunodeficient, or undergoing any form of treatment known to cause immunosuppression
12. Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily treated, subjects can enter the trial)
13. Clinically significant and unexplained elevated liver or renal function tests
14. Female subjects who are pregnant or lactating or refuse to commit to use contraception during the trial
15. Any other significant disease or other clinical findings which in the opinion of the investigator would prevent trial entry
16. History of malignancy of other organ system within past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ≤pT2 upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also subjects with genitourinary cancers other than urothelial cancer or prostate cancer, and subjects with renal mass ≤3 cm that are under active surveillance are excluded (see inclusion criterion 10)
17. Subjects who cannot hold instillation for 1 hour
18. Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
19. Intravesical therapy within 8 weeks prior to beginning IMP with the exception of: • Cytotoxic agents (e.g., Mitomycin C, doxorubicin, epirubicin and gemcitabine) when administered as a single instillation immediately following a TURBT procedure, which is permitted within 70 days prior to beginning trial treatment • Previous intravesical BCG therapy, which can be given ≥5 weeks prior to the biopsy that is required for trial entry

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response ([CR] at any time from first treatment defined as absence of high-grade (HG) recurrence)

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ferring Pharmaceuticals A/S

Sponsor organisation

Ferring Pharmaceuticals A/S

Address

Amager Strandvej 405

City

Kastrup

Postcode

2770

Country

Denmark

Scientific contact point

Organisation

Ferring Pharmaceuticals A/S

Contact name

Kristian Juul

Public contact point

Organisation

Ferring Pharmaceuticals A/S

Contact name

Clinical and Translational Sciences

Third parties 1

Locations

5 EU/EEA countries · 35 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 115 files

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

Application history

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