Vicinium demonstrates efficacy in nonmuscle-invasive bladder cancer

Vicinium induced clinically meaningful complete responses among patients with high-grade nonmuscle-invasive bladder cancer who were unresponsive to bacillus Calmette-Guérin, according to preliminary efficacy data from the ongoing phase 3 VISTA registration trial reported by the drug’s manufacturer.

Vicinium (VB4-845, Sesen Bio) — a locally administered fusion protein — also appeared well tolerated.

“Nonmuscle-invasive bladder cancer is a very prevalent cancer that can progress to become incurable. The usual treatment for patients who relapse or become refractory to bacillus Calmette-Guérin [BCG], today’s standard of care, is complete bladder removal or radical cystectomy,” Michael A.S. Jewett, MD, professor of surgery in the division of urology at University of Toronto, said in a press release. “Removing the bladder is a potentially morbid and complex surgery with potential for side effects that can drastically reduce a patient’s quality of life. In fact, many patients choose not to undergo bladder removal.

“Based on the strength of the clinical activity observed, and the consistently favorable safety and tolerability, I believe that vicinium has the potential to change the treatment outcome for patients,” he added.

The single-arm, multicenter VISTA trial included 133 patients enrolled into one of three cohorts:

patients with carcinoma in situ with or without papillary disease whose cancer was determined to be refractory or recurred within 6 months of BCG (cohort 1; n = 86);
patients with carcinoma in situ with or without papillary disease whose cancer was determined to be refractory or recurred between 6 months and 12 months after BCG (cohort 2; n = 7); and
patients with papillary disease without carcinoma in situ whose cancer appeared refractory or recurred within 6 months of BCG (cohort 3; n = 40).

Complete response rate and duration of response of patients in cohort 1 served as the study’s primary endpoint. Researchers also have presented data on cohort 2, based on FDA guidance on treatment of BCG-unresponsive carcinoma in-situ patients, and data from cohort 3 may serve as an opportunity for future label expansion.

Data from cohort 1 showed complete response rates of 37% at 3 months, 25% at 6 months, 18% at 9 months and 14% at 12 months.

Complete response rates from cohort 2 were 57% at 3 months and 6 months, 43% at 9 months and 14% at 12 months.

Pooling data from these two cohorts, researchers noted the complete response rates are similar to those observed in a prior phase 2 trial.

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Preliminary data from cohort 3 show complete response rates of 39% at 3 months, 27% at 6 months, 20% at 9 months and 14% at 12 months.

Median duration of response has not yet been reached. However, data at this time suggest that vicinium may delay time to radical cystectomy, a key secondary endpoint of the trial, according to the release.

Researchers noted that 78% of adverse events were grade 1 or grade 2. The most commonly reported treatment-related adverse events were dysuria (13%), hematuria (12%) and urinary tract infection (11%).

Fourteen percent of patients experienced serious adverse events, and researchers reported four treatment-related serious adverse events in three patients, including acute renal injury (grade 3), pyrexia (grade 2), cholestatic hepatitis (grade 4) and renal failure (grade 5).

“The design of the VISTA trial aligns with FDA’s guidance for nonmuscle-invasive bladder cancer drug development, and the findings are highly encouraging, demonstrating that treatment with vicinium results in clinically meaningful efficacy and favorable safety and tolerability,” Thomas Cannell, DVM, president and CEO of Sesen Bio, said in the release. “Overall, the data reinforce our belief that vicinium is positioned to provide a valuable benefit to patients by treating their disease with long-term responses and extending their time to face such a decision as removing their bladder.”