A Study of NDV-01 (Sustained-release Gemcitabine-docetaxel) in Participants With Non-muscle Invasive Bladder Cancer

Cohort 1 Inclusion Criteria:

1. Be ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place) at the time of informed consent.
2. Have a histologically confirmed diagnosis (within 90 days of randomization) of IR NMIBC based on the AUA/SUO criteria of IR NMIBC (excluding LGT1 tumors).
3. Participant must be willing to undergo all study procedures (e.g., multiple cystoscopies from Screening through the end of study and TURBT for assessment of recurrence/progression) and receive the assigned treatment, including intravesical chemotherapy if randomized into that arm.
4. Participant must have ≥ 1 IBCG risk factors: 1) multiple tumors, 2) early recurrence (within 1 year), 3) frequent recurrences (> 1 per year), 4) tumor size (> 3 cm), 5) failure of prior induction intravesical therapy.

5. Visible papillary disease must be fully resected prior to randomization, and absence of disease must be documented at Screening cystoscopy. The same method for visualizing disease at Screening cystoscopy should be used throughout for the participant (white light versus enhanced cystoscopic method [e.g., blue light cystoscopy, narrow-band imaging]).

   All pathology specimens must be predominantly urothelial (transitional cell) and have less than 20% variant (e.g., sarcomatoid, squamous component) histology.

6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Cohort 1 Exclusion Criteria:

1. Histologically confirmed stage T1 tumors.
2. Histologically confirmed diagnosis of HR NMIBC (including CIS) or muscle-invasive bladder cancer (MIBC), locally advanced, nonresectable, or metastatic urothelial carcinoma at any time prior to enrollment.
3. Has had urothelial carcinoma outside of the urinary bladder (including prostatic urethra, ureter, or renal pelvis) or has a predominant histological variant of urothelial carcinoma (UC). Ta/any T1, CIS of the upper urinary tract is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study.
4. Participant has tumor(s) involving the prostatic urethra (ductal or stromal).
5. N+ and/or M+ per computed tomography (CT)/magnetic resonance (MR) urography.
6. Received an investigational treatment for bladder cancer within 6 months prior to randomization, before the planned first dose of study treatment, or is currently enrolled in an investigational study.
7. Received adjuvant induction intravesical chemotherapy within 3 months of current diagnosis. Peri-operative instillation of a single dose of intravesical chemotherapy is allowed per institutional guidelines.
8. Received prior intravesical treatment with immunotherapy, including BCG, within 3 months prior to randomization.

Cohort 2 Inclusion Criteria:

1. Cohort 2a: BCG-unresponsive NMIBC with CIS of the bladder, with or without coexisting papillary Ta/T1 tumor(s) who are ineligible for or have elected not to undergo cystectomy at the time of enrollment and have received 1 or 2 lines of therapy after meeting criteria for BCG unresponsiveness and experienced biopsy confirmed CIS disease within 12 months of last treatment, where:

   • Adequate BCG regimen consists of at least 2 courses of BCG, where the first course (induction) must have included at least 5 of 6 doses and the second course may have included a re-induction (at least 2 of 6 treatments) or maintenance (at least 2 of 3 doses). Adequacy of the BCG regimen will be determined by the Investigator in conjunction with the Sponsor.
   • Treatment after BCG unresponsiveness includes either approved or in development therapy
   • Post-treatment presence of CIS must be documented or indicated by pathology at screening or within 4 months of screening (provided no therapy for CIS disease was given after the most recent biopsy).
   • For inclusion, a participant with BCG-unresponsive disease (as defined above) must have received up to two lines of therapy for BCG-unresponsive disease and who are being considered for radical cystectomy. Such therapies may include agents approved or in development (e.g., pembrolizumab, nadofaragene firodenovec, nogapendekin alfa inbakicept-pmln, cretostimogene grenadenorepvec, detalimogene voraplasmid, TARA-002, gemcitabine intravesical system (INLEXZO®), gemcitabine-docetaxel, gemcitabine, MMC, or valrubicin monotherapy. Participant will have demonstrated biopsy-proven recurrence with HG papillary disease (without CIS) after one or two first-line therapy(ies).

2. Cohort 2b: BCG-unresponsive NMIBC of the bladder, with papillary Ta/T1 tumor(s) and without co-existing CIS, who are ineligible for or have elected not to undergo cystectomy at the time of enrollment and have experienced recurrent Ta/T1 disease within 12 months of treatment with 1 or 2 lines of therapy after BCG-unresponsive status.

   • For inclusion, a participant with BCG-unresponsive disease (as defined above) must have received up to two lines of therapy for BCG-unresponsive disease and who are being considered for radical cystectomy. Such therapies may include agents approved or in development (e.g., pembrolizumab, nadofaragene firodenovec, nogapendekin alfa inbakicept-pmln, cretostimogene grenadenorepvec, detalimogene voraplasmid, TARA-002, gemcitabine intravesical system (INLEXZO®), gemcitabine-docetaxel, gemcitabine, MMC, or valrubicin monotherapy. Participant will have demonstrated biopsy-proven recurrence with HG papillary disease (without CIS) after one or two first-line therapy(ies).

All Cohort 2

1. A participant with HG T1 may be eligible after repeat-TURBT showing non-invasive (Ta or less) or no disease. Either original or repeat-TURBT must confirm that muscularis propria is present and uninvolved in the specimen.
2. All specimens must be predominantly urothelial (transitional cell) carcinoma with or without squamous or glandular differentiation. Pure squamous or glandular tumors will not be included. A participant with less than 10% micropapillary histology will be included. All other variant histology (e.g., plasmacytoid, small cell, nested, trophoblastic variants) will not be included.

Cohort 2 Exclusion Criteria:

1. Has had urothelial carcinoma outside of the urinary bladder (i.e., urethra, ureter, or renal pelvis) or has a predominant histological variant of UC. Ta/any T1, CIS of the upper urinary tract is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study and is considered to be without evidence of recurrent disease.

   • Participants have tumor(s) involving the prostatic urethra (ductal or stromal).
   • N+ and/or M+ per computerized tomography (CT)/Magnetic Resonance Imagery (MR) urography.
2. History of prior T2/T3 urothelial carcinoma of the bladder.
3. Concurrent treatment with any chemotherapeutic agent.
4. Intravesical chemotherapy within 3 months of enrollment (including INLEXZO®, gemcitabine-docetaxel)