Introduction:

Sequential intravesical gemcitabine and docetaxel (Gem/Doce) represents a promising option to treat patients with high-risk NMIBC – including those who are BCG-naïve, -exposed and -unresponsive. Gem/Doce is not available in a sustained-release formulation, limiting intravesical exposure.  NDV-01 is an investigational intravesical agent designed for sustained release of Gem/Doce continuously over a 10-day period. NDV-01 may also help overcome the burdens to patient and to provider (e.g. time toxicity) of traditional Gem/Doce. NDV-01 does not require a specialized pharmacy or hood.

Methods:

The study is a single-arm, open-label trial of NDV-01 in participants with HG NMIBC. Participants were given 6 bi-weekly instillations followed by monthly maintenance instillations through month 12.  Complete response (CR) is defined as a negative cystoscopy, cytology, and biopsy (if indicated). The first assessment for CR was evaluated at 3 months.  Participants with a non-CR at 3 months, were eligible to be reinduced with an additional 6 bi-weekly course of therapy.  Disease assessments for CR were also performed at 6, 9, and 12 months. Twenty-three participants have reached the first disease assessment (3-months follow-up) and are included in the per-protocol efficacy analysis. (Five participants are pending their first response assessment.) All 29 participants who have received >= 1 treatment are included in the safety analysis.

Results:

Baseline characteristics of the 29 enrolled participants are shown in Table 1. All participants were ECOG 0-1. Of the 28 participants who received >= 1 dose of NDV-01, 21 (72%) had a TRAE (77% dysuria, 9% asymptomatic positive urine culture, 4% hematuria). No participant had >= Grade 3 TRAE and no participants discontinued treatment due to AEs. Response rates in the 23 participants who received >= 3-month disease assessment are shown in table 2. One participant has reached the 9-month assessment and had a CR. No participant had progression to muscle invasive disease. No participant underwent a radical cystectomy.

Conclusion:

NDV-01 is a novel sustained formulation of Gem/Doce for intravesical use. NDV-01 provides excellent 6-month safety and efficacy in participants with high-risk NMIBC -- including those who are BCG-naïve, -exposed and -unresponsive. The study remains ongoing to provide longer term follow-up and a larger sample size.

Funding: Relmada Therapeutics