Abstract
Intravesical delivery of rAd-IFNα/Syn3 is safe and achieves durable responses in high-grade NMIBC.
Major finding: Intravesical delivery of rAd-IFNα/Syn3 is safe and achieves durable responses in high-grade NMIBC.
Approach: An open-label phase II randomized trial evaluated the safety and activity of rAd-IFNα/Syn3.
Impact: rAd-IFNα/Syn3 warrants further investigation to treat BCG-refractory NMIBC tumors.
Bacillus Calmette-Guerin (BCG) is the standard-of-care treatment for patients with high-grade non–muscle invasive bladder cancer (NMIBC) who are at high risk for recurrence and progression. However, 30% of patients with NMIBC exhibit no response to BCG, over half of patients relapse and progress after BCG treatment, and most patients are unwilling to undergo radical cystectomy. Shore and colleagues evaluated the activity and safety of intravesical delivery of recombinant adenovirus (rAd)-IFNα with Syn3 in a multicenter, open-label, parallel-arm, phase II study. A total of 40 patients with BCG-refractory or relapsed NMIBC were treated with either high-dose (19 patients) or low-dose (21 patients) rAd-IFNα/Syn3. The primary endpoint was relapse-free survival (RFS) at 12 months, and secondary endpoints included safety and tolerability of high- and low-dose rAd-IFNα/Syn3, levels of IFNα-2b in urine, and RFS at 3, 6, and 9 months. Objective responses were achieved in 7 patients (33.3%) in the low-dose group and 7 patients (36.8%) in the high-dose group, all of whom exhibited RFS at 12 months, and the median time to recurrence was 3.52 months for the low-dose group and 11.73 months for the high-dose group. Responses were durable; 8 of 11 patients remained disease-free for at least 15 months. Measurable levels of urine IFNα-2b were noted in month 1 in all patients after a single dose and in month 4 in patients who had received a second dose, but did not correlate with dose or response. rAd-IFNα/Syn3 was well tolerated, although 19 drug-related grade 3 events occurred in 9 patients (22%) and 10 severe adverse events occurred in 5 patients (12.5%), which were resolved with medical therapy. Taken together, the results of this phase II trial suggest that intravesical delivery of rAd-IFNα/Syn3 is safe and has durable antitumor activity in patients with BCG-refractory or relapsed NMIBC, supporting further investigation of rAd-IFNα/Syn3 alone or in combination with other therapies.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.
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