AUA 2020: Phase 3 Results Of Vicinium In BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

(UroToday.com) Most patients newly diagnosed with bladder cancer have non-muscle invasive disease (NMIBC). For patients with intermediate or high-risk NMIBC and those with carcinoma in situ (CIS), adjuvant treatment with Bacille Calmette-Guérin (BCG) is guideline-recommended on the basis of proven benefits in disease recurrence. While BCG is efficacious, many patients eventually develop BCG-unresponsive disease.  For many years, there have been very limited options for these patients. Radical cystectomy has remained the gold standard through numerous approaches including intravesical and systemic therapies have been investigated. One of the alternatively to radical cystectomy in patients with BCG-unresponsive NMIBC is vicinium, a recombinant fusion protein comprised of an anti-EpCAM scFv linked to a variant of Pseudomonas exotoxin A (ETA). ETA mediates tumor cell death by blocking protein synthesis. Dying tumor cells display immunogenic cell death signals and neo-antigens known to promote an adaptive T-cell mediated anti-tumor response. In a podium presentation at the American Urologic Association Virtual Annual Meeting, Neal Shore, MD, FACS, and colleagues presented results of a phase 3 trial of vicinium in patients with BCG-unresponsive NMIBC (NCT02449239).

In a phase 3, single-arm multicenter registrational trial, the authors accrued patients with BCG-unresponsive NMIBC, defined as refractory or relapsing within 6 months (n = 126) and relapsing within 6 to 11 months (n = 7) after adequate BCG therapy. As with BCG, vicinium was administered in an induction phase followed by maintenance. During induction, vicinium was instilled for 2 hours twice weekly for 6 weeks, then weekly for 6 weeks. Disease-free patients at 3 months received maintenance every 2 weeks for up to 2 years. Patients were assessed every 13 weeks, with a response defined as negative cytology along with normal cystoscopy or absence of high-grade disease on biopsy.

With a data cut off of May 29th, 2019, in patients with CIS (n-89), the authors demonstrated a complete response rate at 3-months of 40%. For those with a complete response, the median duration of response was 9.4 months (95% CI, 5.1-NE) and 52% remained disease-free for 12 months after starting treatment.

In patients with papillary disease (n=38), the recurrence-free rates at 3, 6, 12, and 24 months were 71, 58, 50, and 37%, respectively. The median time to recurrence was 13.2 months (95% CI, 5.6-NE). 

Overall, patients who responded at 3 months avoided radical cystectomy for much longer than those who did not respond: 34.0 vs. 20.7 months (p ≤ 0.001). Furthermore, the rate of cystectomy was only 10% (6 of 63) for patients who demonstrated response at 3-month versus 32% (18 of 56) for the non-responders. 

While data remain immature, overall survival was 96% (95% CI, 92-100) at 2 years. 

With respect to toxicity, vicinium was generally well-tolerated with 52% of patients experiencing treatment-related adverse events (AEs), the majority being grade 1-2, without significant differences between age groups. Three patients experienced four treatment-related severe AEs, including grade 4 cholestatic hepatitis, grade 5 renal failure, grade 3 acute kidney injury, and grade 2 pyrexia. Only 3% of the patients discontinued treatment due to AEs.

These data add vicinium to the rapidly growing armamentarium for patients with BCG-unresponsive NMIBC and may allow patients to delay radical cystectomy.

Presented by: Neal Shore, MD, FACS, Medical Director for the Carolina Urologic Research Center, Myrtle Beach, South Carolina

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, TN, USA, Twitter: @WallisCJD, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27-28, 2020.

Related Content: 
Clinical Trial Information: NCT02449239 — Open-Label, Multicenter, Ph 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG

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