Low-grade UTUC Treated With Nadofaragene Firadenovec Administered to the Renal Pelvis (LUNAR)

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

Decision date (initial)

2025-09-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514360-70-00

WHO UTN

U1111-1292-0846

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

• To evaluate the safety and tolerability of nadofaragene firadenovec instilled into the renal pelvis in subjects with low-grade upper tract urothelial carcinoma (LG-UTUC).
• To evaluate the efficacy of nadofaragene firadenovec instilled into the renal pelvis in subjects with LG-UTUC.

Conditions and MedDRA coding

Low-grade upper track urothelial carcinoma (LG-UTUC)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Aged ≥18 years at the time of signing informed consent.
2. Able to give written informed consent.
3. Have biopsy-proven low-grade upper tract urothelial cancer (LG-UTUC) confirmed by a pathology report ≤2 months prior to enrolment.
4. Have ≥1 measurable papillary low-grade tumour (5-15 mm in maximum diameter), evaluated visually above the ureteropelvic junction before enrolment. • Subjects 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.
5. Willing to be available for at least 18 months after first dosing.
6. Have life expectancy >2 years, in the opinion of the investigator.
7. Have an Eastern Cooperative Oncology Group (ECOG) status of 2 or less.
8. 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.
9. 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.
10. Adequate laboratory values: • haemoglobin ≥10 g/dL • white blood cells (WBC) ≥4000/µL • absolute neutrophil count (ANC) ≥2000/µL • platelet count ≥100,000/µL • international normalized ratio (INR)* below institutional upper limit of normal (ULN) • activated partial thromboplastin time (aPTT)* below institutional ULN • aspartate aminotransferase (AST) ≤1.5 x ULN • alanine aminotransferase (ALT) ≤1.5 x ULN • total bilirubin ≤1.5 x ULN • sodium >135 mmol/L • potassium 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.
11. 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]).

Exclusion criteria 21

1. UTUC characterised by one or more of the following: • High-grade cytology or high-grade histology • Multi-focal UTUC - Exception: 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. • Bilateral disease - Exception: 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.
2. Suspected and/or a medical history of hypersensitivity to nadofaragene firadenovec, interferon-α2b (IFN α2b) and/or adenovector medications.
3. Urinary tract infection or bacterial cystitis (once satisfactorily treated, subjects can enter the trial).
4. Clinically significant and unexplained elevated liver or renal function tests at screening.
5. Women who are pregnant (highly sensitive urine or serum pregnancy test at screening) or breastfeeding.
6. Any other significant disease or other clinical findings which in the opinion of the investigator would prevent trial entry.
7. 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: • Treated basal cell carcinoma or squamous cell carcinoma of the skin. • History of ≤pT2 upper tract urothelial carcinoma, at least 24 months after radical nephroureterectomy (RNU). • Cervical intraepithelial carcinoma (CIN) without evidence of invasive carcinoma. • Prostate cancer that is under active surveillance or urothelial cancer. All other genitourinary cancers are excluded.
8. Inability to deliver IMP to the pyelocaliceal system.
9. Previous BCG treatment during 6 months before the initiation of treatment.
10. Any immunosuppressive therapy within 3 months prior to screening.
11. Subjects who are immunocompromised or immunodeficient at screening.
12. Current or previous evidence of carcinoma in situ, of muscle invasive (muscularis propria) urothelial cancer in the urogenital tract presented at the screening visit.
13. Subjects with solitary kidney and/or an eGFR <60 mL/min/1.73 m2 (only applicable for subjects in the safety lead-in period).
14. Concomitant lower tract urothelial carcinoma and/or concomitant or prior urothelial carcinoma within the prostatic urethra.
15. History of high grade papillary urothelial cancer within 2 years prior to screening.
16. Current or prior treatment with mitomycin gel and/or any investigational drug for the treatment of UTUC.
17. Current systemic chemo- or immunotherapy for bladder cancer or any other malignancy.
18. 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.
19. Current or prior retroperitoneal external beam radiotherapy within 5 years of screening.
20. Prior treatment with adenovirus-based drugs including use of other adenovirus vector medications, including COVID-19 vaccines, within 2 weeks before instillation.
21. Hypersensitivity to contrast media used for pyelography.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary Safety Endpoint: The number of treatment-emergent adverse events reported by each subject during the trial.
2. 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)

Investigational products

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

Test 1

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

Oliver Patschan

Public contact point

Organisation

Ferring Pharmaceuticals A/S

Contact name

Clinical and Translational Sciences

Third parties 1

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 38 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