Promising phase 1/2 data surface on novel therapy for treatment of BCG-unresponsive NMIBC

Preliminary results from the LEGEND study (NCT04752722) demonstrate high tolerability and safety of the novel intravesical monotherapy, EG-70, in treating patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC).¹

At 3 months, 83% of patients (5/6) who received EG-70 achieved complete response (CR), according to the treatment manufacturer, enGene.²

"EG-70 was designed ab initio as an intravesical monotherapy that would slot directly into current medical practice to provide ease-of-use and increased access to patients,” said Jason Hanson, JD, CEO of enGene, in a recent news release.² “With the initial results providing a clear best-in-class trajectory, we are confident that EG-70 will be the organ-sparing solution that is a game-changer for patients and physicians.”

This open-label, multicenter study enrolled 222 patients in April 2021. Patient criteria included those with BCG-unresponsive NMIBC with carcinoma in situ (CIS) who were recommended radical cystectomy, those with NMIBC with CIS who were recommended radical cystectomy, or those who had previously been treated with at least 1 dose of intravesical therapy at transurethral resection of the bladder tumor (eligible at 1 month post-surgery). All patients were at least 18 years of age and had an ECOG score of 0,1, or 2, among other inclusion criteria.

Patients were excluded if they had any other malignancy within 1 year of study entry, had concurrent treatment with any chemotherapeutic agent, had a history of other conditions, such as vesicoureteral reflux, or had a history of other treatments such as external beam radiation therapy, among other exclusion criteria.

In phase 1, patients received up to 4 cycles of 50 mL EG-70 via catheter with a targeted retention of 60 minutes. Each cycle lasts about 12 weeks with either 2-day dosing at either Day 1 and Day 8, or 4-day dosing at Day 1, Day 8, Day 29, and Day 36.

The primary outcomes of this phase are nature, incidence, relatedness, and severity of all adverse events and serious adverse events. The secondary outcomes are number of patients who experienced a dose-limiting toxicity through the end of cycle 1 (1 year), and complete response (CR) rate to EG-70 by cystoscopy at 12 weeks.

In phase 2, patients were separated in 2 cohorts. Cohort 1 consisted of patients with BCG-unresponsive NMIBC who were recommended phase 2 dose (RP2D) of up to 4 cycles of EG-70 treatment. Cohort 2 consisted of patients with high-risk NMIBC who did not receive a complete treatment or had never received a treatment of BCG and were RP2D. Patients in these cohorts will receive the same treatment as administered in phase 1.

In addition to monitoring the primary outcome of phase 1, another outcome that will be studied in phase 2 is percentage of patients with cystoscopic CR at 48 weeks. The secondary outcomes are progression-free survival at 4 years, CR rate at 12, 24, 36, and 96 weeks, and duration of response of responding patients at 3 years.

The estimated study completion date is February 2026.

Gary D. Steinberg, MD

"The responses observed with EG-70 are an important step towards NMIBC patients avoiding radical cystectomy," said principal investigator, Gary D. Steinberg, MD. "If similar results are observed as the study progresses, I am confident that this novel intravesical monotherapy will make a meaningful impact in the lives of patients with high risk NMIBC.”

References

1. EG-70 in NMIBC patients who are BCG-unresponsive and high-risk NMIBC patients who have been incompletely treated with BCG or are BCG-naïve (LEGEND STUDY). ClinicalTrials.gov. Last updated January 24, 2022. Accessed February 10, 2022. https://clinicaltrials.gov/ct2/show/NCT04752722?term=nct04752722&draw=2&rank=1

2. enGene announces positive preliminary phase 1/2 data with EG-70 in BCG-unresponsive non-muscle invasive bladder cancer. Cision PR Newswire. Published February 8, 2022. Accessed February 10, 2022. https://www.prnewswire.com/news-releases/engene-announces-positive-preliminary-phase-12-data-with-eg-70-in-bcg-unresponsive-non-muscle-invasive-bladder-cancer-301477766.html