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
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

1. Eastern Cooperative Oncology Group (ECOG) status ≤2
2. Aged ≥18 years at the time of consent
3. Available for the whole duration of the trial
4. Life expectancy >2 years, in the opinion of the investigator
5. 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

1. Subjects who elect not to undergo cystectomy
2. 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 15)
3. 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 effective contraception during treatment with the investigational medicinal product (IMP) and for 6months following the last dose. Otherwise, female subjects must be post-menopausal (no menstrual period for a minimum of 12months), as confirmed by follicle-stimulating hormone levels) or surgically sterile.

12.Male subjects must use highly effective contraception and a condom during sexual contact regardless of partner’s childbearing potential, until 3months following the last trial drug administration. Effective contraception is specified in inclusion criterion 11.

1. Adequate laboratory values:

4.1.2

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:
2. Current systemic therapy for bladder cancer other than IMP used in randomization arm
3. Current or p