NCT06668493招募中1 期
A Phase 1/2, Single-arm, Open-Label Trial to Evaluate the Safety and Efficacy of Nadofaragene Firadenovec Instilled to the Renal Pelvis in Adult Subjects With Low-grade Upper Tract Urothelial Carcinoma (LG-UTUC)
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 13
- 主要终点
- The number of treatment-emergent adverse events reported by each subject during the trial.
研究概览
简要总结
The primary purpose of this trial is to evaluate the safety & tolerability of Nadofaragene Firadenovec in subjects with LG-UTUC. To help with this evaluation, a safety lead-in period will be conducted for the first 6 subjects. Complete response is at 3 or 6 months defined as absence of any UTUC in the renal pelvis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥18 years at the time of signing informed consent.
- •Able to give written informed consent.
- •Have biopsy-proven low-grade upper tract urothelial cancer (LG-UTUC) confirmed by a pathology report ≤2 months prior to enrolment.
- •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.
- •Willing to be available for at least 18 months after first dosing.
- •Have life expectancy >2 years, in the opinion of the investigator.
- •Have an Eastern Cooperative Oncology Group (ECOG) status of 2 or less.
- •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 postmenopausal (no menstrual period for a minimum of 12 months) 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.
- •Male subjects with female partners of reproductive potential must be surgically sterile or willing to use a condom in addition to effective contraception in their female partner during treatment with the IMP and for 3 months following the last dose.
- •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
- •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
排除标准
- •Exclusion Criteria:
- •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.
- •Current or previous evidence of carcinoma in situ, of muscle invasive (muscularis propria) urothelial cancer in the urogenital tract presented at the screening visit.
- •Concomitant lower tract urothelial carcinoma and/or concomitant or prior urothelial carcinoma within the prostatic urethra.
- •History of high grade papillary urothelial cancer within 2 years prior to screening.
- •Current or prior treatment with mitomycin gel and/or any investigational drug for the treatment of UTUC.
- •Current systemic chemo- or immunotherapy for bladder cancer or any other malignancy.
- •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.
- •Current or prior retroperitoneal external beam radiotherapy within 5 years of screening.
- •Prior treatment with adenovirus-based drugs including use of other adenovirus vector medications, including COVID-19 vaccines, within 2 weeks before instillation.
- •Suspected and/or a medical history of hypersensitivity to nadofaragene firadenovec, interferon-α2b (IFN-α2b) and/or adenovector medications.
- •Urinary tract infection or bacterial cystitis (once satisfactorily treated, subjects can enter the trial).
- •Clinically significant and unexplained elevated liver or renal function tests at screening.
- •Women who are pregnant (highly sensitive urine or serum pregnancy test at screening) or breastfeeding.
- •Any other significant disease or other clinical findings which in the opinion of the investigator would prevent trial entry.
- •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.
- •Inability to deliver IMP to the pyelocaliceal system.
- •Previous BCG treatment during 6 months before the initiation of treatment.
- •Any immunosuppressive therapy within 3 months prior to screening.
- •Subjects who are immunocompromised or immunodeficient at screening.
- •Subjects with solitary kidney and/or an eGFR <60 mL/min/1.73 m2 (only applicable for subjects in the safety lead-in period).
研究组 & 干预措施
Treatment
Experimental
干预措施: Nadofaragene Firadenovec (Drug)
结局指标
主要结局
The number of treatment-emergent adverse events reported by each subject during the trial.
时间窗: Up to 30 months
The number of treatment-emergent adverse events reported by each subject during the trial.
时间窗: Up to 30 months
Complete response
时间窗: Up to 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).
次要结局
- Occurrence of anti-adenoviral antibodies.(Up to 30 months)
- Shedding of adenoviral vector with IFN-α2b.(Before dose and up to 15 days after dose)
- Systemic exposures to adenoviral vector with IFN-α2b.(Before dose and up to 15 days after dose)
- Occurrence of anti-interferon-α2b (IFN-α2b) antibodies.(Up to 30 months)
- Systemic exposures to IFN-α2b protein.(Before dose and up to 15 days after dose)
- Systemic exposures to Syn3NODA.(Before dose and up to 15 days after dose)
- Duration of response, defined as the time from first achieved complete response to disease recurrence, disease progression (defined as any high-grade disease) or disease-specific death, whichever occurs first.(Up to 30 months)
- Urinary excretion of IFN-α2b protein.(Before dose and up to 15 days after dose)
研究者
研究点 (13)
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相关资讯
Real-World Data and Ongoing Trials Highlight Efficacy of Nadofaragene Firadenovec in Bladder Cancer- Real-world data presented at the 2025 ASCO Genitourinary Cancers Symposium indicates nadofaragene firadenovec demonstrates positive efficacy and safety outcomes in treating NMIBC.
- The ABLE-32 phase 3B trial is underway to assess nadofaragene firadenovec in intermediate-risk NMIBC patients, addressing the unmet need for FDA-approved treatments.
- Additional trials, including ABLE-22 and LUNAR, are exploring nadofaragene firadenovec as a monotherapy, in combination with other treatments, and in low-grade upper tract urothelial carcinoma.
- Nadofaragene firadenovec, the first FDA-approved intravesical gene therapy, offers a novel approach by turning bladder wall cells into interferon microfactories to fight cancer.last yearFerring Advances Nadofaragene Firadenovec Clinical Program in Urothelial Cancers- Ferring Pharmaceuticals is expanding the clinical trial program for nadofaragene firadenovec, an intravesical gene therapy, to include intermediate-risk NMIBC and low-grade UTUC.
- A Phase 2 trial (ABLE-22) will evaluate nadofaragene firadenovec alone or with chemotherapy/immunotherapy in high-risk BCG-unresponsive NMIBC, including re-induction for non-responders.
- The Phase 3B ABLE-32 trial will assess nadofaragene firadenovec in intermediate-risk NMIBC, an area with no FDA-approved treatments, using recurrence-free survival as the primary endpoint.
- The LUNAR trial is initiated to study nadofaragene firadenovec in patients with low-grade upper tract urothelial cancer (UTUC), addressing a significant unmet need.last year