Gene therapy EG-70 shows early promise in BCG-unresponsive NMIBC

Nearly three-fourths of patients with non–muscle invasive bladder cancer (NMIBC) had a complete response to the novel gene therapy EG-70, according to preliminary data from the phase 1/2 LEGEND trial (NCT04752722) shared during the 2023 ASCO Genitourinary (GU) Cancers Symposium.^1,2

Patients had received an average of 11 prior doses of BCG.

“EG-70 is a novel non-viral gene therapy encoding 2 RIG-I agonists to stimulate the innate immune system, and IL-12 to stimulate the adaptive immune system,” enGene Inc, the developer of the investigational treatment, explained in a press release.²

The phase 1 part of the study presented at ASCO GU included patients with NMIBC with carcinoma in situ who were unresponsive to bacillus Calmette-Guérin (BCG) therapy. There were 20 patients enrolled who received at least 1 dose of EG-70 and all 20 were included in the safety population. The intent-to-treat cohort, which comprised the efficacy population, included 17 of the 20 patients.

At baseline, the mean patient age was 72 years and the mean BMI was 28.4. Patients were mostly male (80%) and White (95%) and had received an average of 11 prior doses of BCG.

Patients received either 2 or 4 doses of EG-70 in a 12-week cycle. The study had a 3+3 dose escalation design with a total of 4 possible dose levels.

Regarding safety, lead study author Gary Steinberg MD, professor at the Perlmutter Cancer Center and Department of Urology and director of the Goldstein Urology Bladder Cancer Program of NYU Langone Health, said during the meeting, “EG-70 was generally safe and well-tolerated. Adverse events have been largely consistent with urinary tract instrumentation and were not dose related.”

Overall, 13 (65%) of 20 patients experienced at least 1 treatment-emergent adverse event (TEAE) that was considered to be related to the study treatment. All were grade 1/2 except 1 patient with a grade 3 TEAE (renal failure) that was considered at the time of the study to be possibly related to EG-70. This grade 3 TEAE led to discontinuation of study treatment.

“On review of the baseline CT scans and medical records, however, it was observed that the renal failure was observed at baseline before treatment with EG-70,” Steinberg noted during his meeting presentation.

Efficacy results showed that 12 (71%) of 17 patients had a complete response. Further, 82% of the efficacy population (14 of 17 patients) continued on EG-70 past 3 months.

Following the positive results in phase 1, the phase 2 part of the study is schedule to launch by the middle of this year.

"While the data are still early, EG-70's safety profile and efficacy are well on their way toward establishing a new benchmark for monotherapy treatment of high-risk NMIBC with BCG-unresponsive carcinoma in situ," Steinberg stated in a press release.² "If these trends continue into phase 2, I am optimistic that EG-70 will become an important, useful, and innovative tool in the fight against NMIBC, especially given its non-viral nature and relative ease of handling and use."

References

1. Steinberg GD, Kalota SJ, Lotan Y, Warner L, Dauphinee S, Mazanet R. Clinical results of a phase 1 study of intravesical EG-70 in patients with BCG-unresponsive NMIBC. J Clin Oncol 41, 2023 (suppl 6; abstr 512).

2. enGene announces poster presentation containing interim Phase 1 clinical trial data at the 2023 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Published online February 14, 2023. Accessed February 27, 2023. https://prn.to/3KLa6CS