Trial evaluates combination of NAI plus BCG for treatment of NMIBC

"I think NAI plus BCG will be a game-changer in the community, probably more than it would be in academic medical settings," says Karim Chamie, MD.

In this interview, Karim Chamie, MD, highlights interim findings from an ongoing study (NCT03022825) looking at the safety and efficacy of combining Nogapendekin alfa inbakicept (NAI; N-803) with BCG intravesical instillation for the treatment of BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC).1 Chamie is an associate professor of urology at the University of California, Los Angeles.

Could you describe the background for this study?

Patients with BCG-unresponsive bladder cancer have limited treatment options. [One of] their treatment options can be a radical cystectomy and urinary diversion. Most common in the United States, that's removal of the bladder, the lymph nodes, and the surrounding organs and diverting the urine, in 80% of cases, to an external bag, which we call an ileal conduit or a urostomy. They could also be offered salvage intravesical chemotherapy, such as gemcitabine and docetaxel. Although most patients will have an initial response, the vast majority of patients, if you follow them 2 years out, will develop a recurrence.

The last option is a clinical trial. Due to the limited number of available treatment options, patients often choose the option that provides them with the greatest oncologic efficacy. In this case, it's a radical cystectomy, because it's associated with a 90% or 95% recurrence-free survival.

The problem with that is that it yields significant quality-of-life changes that sometimes patients need to get accustomed to. Sometimes they choose not to go down that road because of fear that that quality of life is not congruent with one that they would wish to proceed with. That's the purpose of initiating a trial in BCG-unresponsive bladder cancer, because it's such an unmet need.

What were some of your notable findings?

What we found was that the complete response rate was very high; it was at 71%. What was most notable was that the median durability of that response was 2 years. This is an impressive finding, as patients now have an option of intravascular therapy that not only offers them a high response rate, but a durable efficacy.

What most patients would look at is, "maybe 71% complete response rates are not 100%, but the fact that half of those patients are still disease free 2 years later, that's important." What's even more important is that about 86% of patients, if you follow them 2 years out, still have their bladders intact. Only 14% of our patients had their bladders removed after 2 years.

This trial is ongoing. What is the estimated timeline for results?

The study has almost completed accrual. There are only a few slots available. The Biologic License Agreement has already been submitted to the FDA for approval, and it's currently being evaluated by the agency. Hopefully, we'll have an answer back by the end of May 2023.

What might further research on this topic cover?

The data are impressive, but there's an opportunity to potentially further augment the efficacy with the combination of other immunotherapeutic agents such as checkpoint inhibitors or other immunomodulatory agents. I think the primary focus will be for patients who have high-risk disease, or patients who failed previous BCG or patients who have high-risk features. [Other studies could look at] potentially combining this drug with other systemic therapies for bladder preservation for patients with muscle-invasive bladder cancer.

What is the take-home message for practicing urologists?

The combination of NAI plus BCG was safe, it was effective, and it serves as a feasible and viable alternative to other agents in this disease space that oftentimes require systemic checkpoint inhibitors or drugs with poor efficacy, such as VALSTAR [valrubicin], or with limited accessibility to community urologists, such as intravesical gemcitabine and docetaxel. For that reason, I think NAI plus BCG will be a game-changer in the community, probably more than it would be in academic medical settings.

Is there anything else that you would like to add?

I think the data speak for themself; the drug is safe, feasible, effective, and I think it opens opportunities to combine this drug with other immunomodulatory agents in similar high-risk patients or in patients who have muscle-invasive disease. I think the future is a lot more promising and brighter than in the past.


1. Chamie K, Chang SS, Kramolowsky E, et al. IL-15 superagonist NAI in BCG-unresponsive non–muscle-invasive bladder cancer. N Engl J Med. Published online November 10, 2022. Accessed December 14, 2022.