A Study of NDV-01 (Sustained-release Gemcitabine-docetaxel) in Participants With Non-muscle Invasive Bladder Cancer
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.
detailed description
The study is comprised of two cohorts, described in the sections that follow.
Cohort 1 (Intermediate Risk)
Cohort 1 is 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. Eligible participants must have IR-NMIBC according to the AUA/Society of Urologic Oncology (SUO) guidelines definition and at least one of the following risk factors: multiple LG tumors (Ta), solitary LG tumor \>3 cm, solitary HG tumor \< 3 cm, early recurrence of LG tumor (\<1 year), frequent recurrence (\>1 per year), or recurrence after prior intravesical chemotherapy. LGT1 tumors are the exception. The IR-NMIBC diagnosis qualifying the participant for the study must be within 90 days of randomization. All participants in Cohort 1 will have undergone TURBT with complete resection of all papillary diseases and will be confirmed to be disease-free within 90 days prior to randomization. All enrolled participants will have histologically confirmed IR-NMIBC.
A target of 276 participants will be randomized 1:1 (N=138 per arm) to treatment with either NDV-01 (Treatment Group) or observation (Control Group). Participants will be stratified based on 1) low-grade vs. high-grade disease and 2) the use of perioperative chemotherapy (Yes/No). Eligible participants should have had a TURBT or tumor excision within 90 days of randomization. The TURBT procedure may include a single dose of perioperative chemotherapy per the Investigators' decision and local standard of care.
Participants in the Treatment Group will have NDV-01 instilled into the bladder via a urethral catheter on Day 1 of the Treatment Phase (i.e., start of Week 0) and NDV-01 will be delivered biweekly for 12 weeks, followed by maintenance therapy once every month for up to 12 months after Day 1.
Participants in the Control Group will be observed with cystoscopy, urinary cytology, and biopsy (if indicated). Participants in the Control Group who demonstrate recurrence will be provided the option for crossover and receive treatment with NDV-01 within 12 weeks of disease recurrence. Crossover participants will begin NDV-01 instillations (within 12 weeks of recurrence) at Treatment Day 1 (see Table 2) and will complete Years 2-3 of the Follow-up Period, or will be discontinued at study closure, whichever occurs first.
Additionally, in the event of a positive study result (compelling results for disease-free survival \[DFS\]) at any of the planned analyses, and upon further notification by the Sponsor at the discretion of the IDMC, participants in the Control Group may have the opportunity to crossover and receive NDV-01 for up to one year.
official title
A Phase 3 Study Evaluating the Efficacy and Safety of NDV-01 in Participants With Non-muscle Invasive Bladder Cancer (RESCUE)