Jen-Jane Liu, MD, outlines progress of LEGEND trial of detalimogene voraplasmid

In this video, Jen-Jane Liu, MD, an associate professor of urology at the Oregon Health & Science University School of Medicine in Portland, discusses the LEGEND trial (NCT04752722) evaluating the investigational treatment detalimogene voraplasmid in patients with high-risk, BCG-unresponsive, non-muscle invasive bladder cancer with carcinoma in situ (CIS). According to Liu, the primary cohort of patients with BCG-unresponsive CIS has reached its target enrollment of 100 participants. Enrollment for the remaining groups—those with BCG-unresponsive papillary-only disease and BCG-exposed patients—remains open but is close to completion.

Preliminary data from the study are promising. The reported anytime response rate is approximately 71%, and among the first 20 evaluable patients, the t3-month complete response rate is around 67%. Liu emphasized, however, that longer-term data will be essential to determine the therapy’s clinical relevance, particularly regarding sustained cancer-free survival at 1 year—a more meaningful measure of efficacy in this patient population.

At present, there are no confirmed expansion cohorts or additional trials exploring detalimogene voraplasmid in other bladder cancer subtypes. Liu noted that it is typical for new intravesical therapies to first target high-risk, BCG-unresponsive or BCG-exposed patients because this aligns with regulatory pathways and current standards of care. Over time, research may expand into intermediate-risk populations or investigate combinations with systemic or other intravesical agents, potentially addressing higher-risk groups such as those with muscle-invasive disease.

Looking ahead, Liu said the most critical next step for the LEGEND trial will be obtaining more mature data from a larger number of patients, particularly in the BCG-unresponsive CIS cohort. These data will help clarify the durability of response and safety profile of detalimogene voraplasmid. With numerous agents now emerging in the intravesical therapy landscape, Liu underscored the need for options that can achieve truly durable responses and offer meaningful alternatives to cystectomy for patients unresponsive to BCG.