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

NCT07464145 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: REL-NDV01-303
• Study Type: interventional
• Target: 393
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study REL-NDV01-303 is a Phase 3, open-label, multi-center study to determine the safety and efficacy of NDV-01 in adult participants with NMIBC. The study will include two cohorts:

• Cohort 1: a randomized, open-label, parallel group, multi-center, Phase 3 study evaluating the efficacy and safety of the NDV-01 versus observation in participants with histologically confirmed IR-NMIBC.
• Cohort 2: an open-label, multi-center, single-arm Phase 3 study evaluating the efficacy and safety of the NDV-01 in two populations of high-risk NMIBC:
• Cohort 2a: will include participants with HR-NMIBC who have a biopsy-proven recurrence with CIS ± papillary disease after receiving one or 2 lines of therapy for BCG-unresponsive NMIBC (approved or in development).
• Cohort 2b: will include participants with high-risk papillary-only disease (without CIS) NMIBC who have a biopsy-proven recurrence with HG papillary disease after receiving one or 2 lines of therapy for BCG-unresponsive NMIBC (approved or in development). This study will evaluate the safety and efficacy of intravesical administration of NDV-01, and its effect on disease recurrence and progression in patients with NMIBC who have IR disease and have recently undergone a TURBT (Cohort 1) and in patients who have HR BCG-unresponsive disease and who have recurred after first-line therapy for BCG-unresponsive patients - both approved and in development - and are unwilling or unable to undergo radical cystectomy (Cohort 2). Both GEM and DOCE have established safety and efficacy across a range of tumor types, including IR and BCG-unresponsive NMIBC. By combining both GEM and DOCE in an intravesical extended-release formulation, Relmada believes that NDV-01 has the potential to be an agent for second-line therapy in patients who have recurred after first-line therapy in BCG-unresponsive disease, thereby avoiding radical cystectomy. This study will serve as a master protocol for all cohorts included in the study.

Conditions

Bladder (Urothelial, Transitional Cell) Cancer; Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive); Urothelial Carcinoma Bladder; Urothelial Carcinoma Recurrent; Urologic Cancer

Keywords

NMIBC; non-muscle-invasive bladder cancer; bladder cancer

Outcome Measures

Primary Outcomes (2)

• Disease Free Survival in participants with Intermediate Risk NMIBC

  Time from randomization to either time of the first recurrence or progression, or death due to any cause, whichever occurs first. It is hypothesized that sustained local delivery of GEM and DOCE (via NDV-01) in participants with IR-NMIBC will result in longer DFS than achieved with observation after TURBT. Under the exponential distribution assumption for DFS, this translates into testing the statistical hypothesis that the hazard ratio is significantly less than 1.0. Primary endpoint will be tested using a one-sided 2.5% level of significance.

  From date of randomization to at least 2 years of follow-up assessing for DFS events.

• To evaluate the efficacy of NDV-01 (determined by complete response [CR] anytime) administered by intravesical instillation in patients with BCG-unresponsive NMIBC who have recurred after first-line intravesical therapy (approved or in development).

  Percentage of participants with CR at anytime based on cystoscopy, urine cytology, and biopsies. Protocol-driven mapping biopsies (as assessed by central pathology) will be performed at 12 months

  From date of randomization through 3 years of follow-up assessing for CR.

Study Arms (3)

Intermediate Risk NMIBC, NDV-01 Treatment Group

EXPERIMENTAL

NDV-01 (sustained-release gemcitabine-docetaxel)

Drug: NDV-01 (sustained-release gemcitabine-docetaxel)

Intermediate Risk NMIBC, Observation Group

NO INTERVENTION

Surveillance with Cystoscopy, Urine Cytology, and Biopsy (if indicated)

BCG-Unresponsive High-Risk NMIBC, NDV-01 Treatment Group

EXPERIMENTAL

NDV-01 (sustained-release gemcitabine-docetaxel)

Drug: NDV-01 (sustained-release gemcitabine-docetaxel)

Interventions

NDV-01 (sustained-release gemcitabine-docetaxel) DRUG

NDV-01 (sustained-release gemcitabine-docetaxel)

BCG-Unresponsive High-Risk NMIBC, NDV-01 Treatment Group; Intermediate Risk NMIBC, NDV-01 Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Histologically confirmed stage T1 tumors.
• 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.
• 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.
• Participant has tumor(s) involving the prostatic urethra (ductal or stromal).
• N+ and/or M+ per computed tomography (CT)/magnetic resonance (MR) urography.
• 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.
• 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.
• Received prior intravesical treatment with immunotherapy, including BCG, within 3 months prior to randomization.
• 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).
• 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.
• All Cohort 2
• 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.

Sponsors & Collaborators

• Relmada Therapeutics, Inc.: lead

Related Publications (3)

• Holzbeierlein JM, Bixler BR, Buckley DI, Chang SS, Holmes R, James AC, Kirkby E, McKiernan JM, Schuckman AK. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment. J Urol. 2024 Apr;211(4):533-538. doi: 10.1097/JU.0000000000003846. Epub 2024 Jan 24.

  PMID: 38265030 BACKGROUND

• Tan WS, McElree IM, Davaro F, Steinberg RL, Bree K, Navai N, Dinney CP, O'Donnell MA, Li R, Kamat AM, Packiam VT. Sequential Intravesical Gemcitabine and Docetaxel is an Alternative to Bacillus Calmette-Guerin for the Treatment of Intermediate-risk Non-muscle-invasive Bladder Cancer. Eur Urol Oncol. 2023 Oct;6(5):531-534. doi: 10.1016/j.euo.2023.06.011. Epub 2023 Jul 18.

  PMID: 37468392 BACKGROUND

• Steinberg RL, Thomas LJ, O'Donnell MA, Nepple KG. Sequential Intravesical Gemcitabine and Docetaxel for the Salvage Treatment of Non-Muscle Invasive Bladder Cancer. Bladder Cancer. 2015 Apr 30;1(1):65-72. doi: 10.3233/BLC-150008.

  PMID: 30561441 BACKGROUND

Related Links

• Description: AUA/SUO Guidelines for NMIBC

MeSH Terms

Conditions

Neoplasms; Urologic Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urinary Bladder Diseases

Study Officials

• Raj S Pruthi, MD MHA FACS

  Relmada Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Tiffany Sepp - Executive Vice President of Clinical Operations

CONTACT

617-710-0770; tsepp@relmada.com

Scott White, MPH - Director of Clinical Operations

CONTACT

646-428-5264; swhite@relmada.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohort 1: randomized, open label, parallel group (NDV-01/standard of care) Cohort 2: open label, single group assignment (NDV-01)

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 11, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2032
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share