NADOFARAGENE FIRADENOVEC for Low-grade upper tract urothelial carcinoma

Inclusion criteria

• {"criterion_text":"- Aged ≥18 years at the time of signing informed consent.\n- Adequate laboratory values: •\thaemoglobin ≥10 g/dL •\twhite blood cells (WBC) ≥4000/µL •\tabsolute neutrophil count (ANC) ≥2000/µL •\tplatelet count ≥100,000/µL •\tinternational normalized ratio (INR)* below institutional upper limit of normal (ULN) •\tactivated partial thromboplastin time (aPTT)* below institutional ULN •\taspartate aminotransferase (AST) ≤1.5 x ULN •\talanine aminotransferase (ALT) ≤1.5 x ULN •\ttotal bilirubin ≤1.5 x ULN •\tsodium >135 mmol/L •\tpotassium between 3.6 and 5.0 mmol/L * 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 regarding their current concomitant anticoagulant therapy.\n- Have an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 (for inclusion in the safety lead-in the eGFR must be ≥60 mL/min/1.73 m2 [see exclusion criteria #‎20‎20]).\n- Able to give written informed consent.\n- Have biopsy-proven low-grade upper tract urothelial cancer (LG-UTUC) confirmed by a pathology report ≤2 months prior to enrolment.\n- Have ≥1 measurable papillary low-grade tumour (5-15 mm in maximum diameter), evaluated visually above the ureteropelvic junction before enrolment. •\tSubjects with low-grade tumour larger than 15 mm will be eligible if endoscopic downsizing of the tumour to 5-15 mm in maximum diameter has been performed before enrolment.\n- Willing to be available for at least 18 months after first dosing.\n- Have life expectancy >2 years, in the opinion of the investigator.\n- Have an Eastern Cooperative Oncology Group (ECOG) status of 2 or less.\n- 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, 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.\n- 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 #‎8."}

Exclusion criteria

• {"criterion_text":"- UTUC characterised by one or more of the following: •\tHigh-grade cytology or high-grade histology •\tMulti-focal UTUC -\tException: Subjects with low-grade multi-focal tumours will be eligible if any ureteral tumours can be ablated before enrolment and if the total diameter of the multifocal tumours above the ureteropelvic junction is not exceeding 15 mm in diameter. •\tBilateral disease -\tException: Subjects who have had bilateral disease are eligible (not in the safety lead-in) if one renal unit is removed or rendered disease-free by endoscopic ablation before enrolment.\n- Any immunosuppressive therapy within 3 months prior to screening.\n- Subjects who are immunocompromised or immunodeficient at screening.\n- Current or previous evidence of carcinoma in situ, of muscle invasive (muscularis propria) urothelial cancer in the urogenital tract presented at the screening visit.\n- Subjects with solitary kidney and/or an eGFR <60 mL/min/1.73 m2 (only applicable for subjects in the safety lead-in period).\n- Concomitant lower tract urothelial carcinoma and/or concomitant or prior urothelial carcinoma within the prostatic urethra.\n- History of high grade papillary urothelial cancer within 2 years prior to screening.\n- Current or prior treatment with mitomycin gel and/or any investigational drug for the treatment of UTUC.\n- Current systemic chemo- or immunotherapy for bladder cancer or any other malignancy.\n- Current or prior investigational treatment for Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) or any other investigational drug within 1 month prior to screening.\n- Current or prior retroperitoneal external beam radiotherapy within 5 years of screening.\n- Suspected and/or a medical history of hypersensitivity to nadofaragene firadenovec, interferon-α2b (IFN α2b) and/or adenovector medications.\n- Prior treatment with adenovirus-based drugs including use of other adenovirus vector medications, including COVID-19 vaccines, within 2 weeks before instillation.\n- Hypersensitivity to contrast media used for pyelography.\n- Urinary tract infection or bacterial cystitis (once satisfactorily treated, subjects can enter the trial).\n- Clinically significant and unexplained elevated liver or renal function tests at screening.\n- Women who are pregnant (highly sensitive urine or serum pregnancy test at screening) or breastfeeding.\n- Any other significant disease or other clinical findings which in the opinion of the investigator would prevent trial entry.\n- History of malignancy in any other organ system than the upper urinary tract within the past 5 years prior to screening. However, subjects with the following exceptions will be allowed inclusion in the trial: •\tTreated basal cell carcinoma or squamous cell carcinoma of the skin. •\tHistory of ≤pT2 upper tract urothelial carcinoma, at least 24 months after radical nephroureterectomy (RNU). •\tCervical intraepithelial carcinoma (CIN) without evidence of invasive carcinoma. •\tProstate cancer that is under active surveillance or urothelial cancer. All other genitourinary cancers are excluded.\n- Inability to deliver IMP to the pyelocaliceal system.\n- Previous BCG treatment during 6 months before the initiation of treatment."}

Primary endpoints

• {"endpoint_text":"- Primary Safety Endpoint: The number of treatment-emergent adverse events reported by each subject during the trial.","definition_or_measurement_approach":"Count of treatment-emergent adverse events reported by each subject during the trial."}
• {"endpoint_text":"- Primary Efficacy Endpoint: Complete response at 3 or 6 months defined as absence of any UTUC in the renal pelvis, i.e. negative urine cytology for high-grade urothelial carcinoma (centrally assessed), and either no suspicious lesions on ureteroscopy (investigator assessed) or a negative for-cause biopsy (centrally assessed)","definition_or_measurement_approach":"Complete response assessed at 3 or 6 months defined by: negative urine cytology for high-grade urothelial carcinoma (central assessment) AND either no suspicious lesions on ureteroscopy (investigator-assessed) OR a negative for-cause biopsy (central assessment)."}

Methods

• Doctor-to-doctor letters (Dr to Dr Letter) for clinician referral (documents present country-specific: ES, NL, FR).
• Doctor-to-patient letters (Dr to Patient Letter) distributed via clinicians to potential participants (documents present country-specific: ES, NL, FR).
• Patient advocacy outreach (Patient Advocacy Intro Letter) to advocacy groups to raise awareness (country-specific materials present: ES, NL, FR).
• Patient brochures and study visit guides for potential participants (Patient Brochure, Study Visit Guide; country-specific materials ES, NL, FR).
• Visit reminder cards for enrolled participants (Visit Reminder Card; country-specific: ES, NL, FR).
• Recruitment arrangements documents (K1) summarising planned recruitment channels and materials (country-specific K1 documents for ES, NL, FR).

Spain

Earliest CTIS Part Ii Submission Date

17-06-2025

Latest Decision Or Authorization Date

22-09-2025

Processing Time Days

97

Number Of Sites

1

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

13-08-2025

Latest Decision Or Authorization Date

16-09-2025

Processing Time Days

34

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

11-07-2025

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

284

Number Of Sites

2

Number Of Participants

1

Primary sponsor

Full Name

Ferring Pharmaceuticals A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Syneos Health Netherlands B.V.

Responsibilities

sponsorDuties codes: 12, 5

Third parties

• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"sponsorDuties codes: 12, 5","organisation_type":"Pharmaceutical company"}