Intravesical rAd–IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin–Refractory or Relapsed Non–Muscle-Invasive Bladder Cancer: A Phase II Randomized Study

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Neal D. Shore, Stephen A. Boorjian, Daniel J. Canter, Kenneth Ogan, Lawrence I. Karsh, Tracy M. Downs, Show More

N.D.S., S.A.B., and D.J.C. contributed equally to the study.

Purpose- Many patients with high-risk non–muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd–IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC.
 
Methods- In this open-label, multicenter (n = 13), parallel-arm, phase II study (ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd–IFNα/Syn3 (randomly assigned 1:1 to 1 × 1011 viral particles (vp)/mL or 3 × 1011 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses.

Results- Forty patients received rAd–IFNα/Syn3 (1 × 1011 vp/mL, n = 21; 3 × 1011 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd–IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%)

Conclusion-  rAd—IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.

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