Sesen Bio Pauses Clinical Development for Vicineum in BCG-Unresponsive NMIBC


The clinical development of Vicineum for use as a potential therapeutic option in patients with high-risk, Bacillus Calmette-Guérin–unresponsive non–muscle invasive bladder cancer.

non-muscle invasive bladder cancer

The clinical development of Vicineum for use as a potential therapeutic option in patients with high-risk, Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC), has been voluntarily paused in the United States, according to an announcement from Sesen Bio.1

The decision follows recent discussions with the FDA, and a comprehensive assessment that was done on the agent, in which the incremental development timeline and associated costs for an additional phase 3 trial of the recombinant fusion protein in those with NMIBC were further evaluated.

The late-stage clinical company shared that this pause in development allows for conservation of cash and the opportunity to continue to evaluate possible strategic alternatives to maximize shareholder value, according to a recent press release.

“We have had 4 productive meetings with the FDA since August 2021, and we believe we have a full understanding of the FDA’s evolving position and guidance on the following variables: accelerated vs standard approval, single-arm vs randomized controlled trials, comparative vs non-comparative efficacy end points, and adequate vs less-than-adequate BCG patient populations,” Thomas Cannell, DVM, president and chief executive officer of Sesen Bio, stated in the press release.

Cannell added that the treatment paradigm for NMIBC has evolved, with a significant uptake of intravesical chemotherapy observed during the BCG shortage. “In assessing the impact of the regulatory and commercial landscape, we have made the decision to pause the clinical development of Vicineum,” Cannell said.

Vicineum is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule antigens on the surface of cancer cells to deliver the protein payload Pseudomonas Exotoxin A. The agent is created with a stable, genetically engineered peptide tether to confirm that the payload remains linked to the antibody-binding fragment until it is internalized by the tumor cell. Notably, the design of the fusion protein is hypothesized to reduce the risk of toxicity to healthy tissues.

Vicineum was examined in patients with NMIBC who previously received standard-of-care BCG as part of the open-label, multicenter, single-arm, phase 3 VISTA trial (NCT02449239).2,3 The trial enrolled those with refractory or relapsed disease post BCG treatment, who had a Karnofsky performance status of 60 or higher and acceptable organ function.

Those with evidence of urethral tract transitional cell carcinoma within 2 years before treatment, or those with hydronephrosis were excluded. Other exclusion criteria included having received any intravesicular or other chemotherapy within 2 weeks of treatment on the trial or any investigational agent within 4 weeks of the initial dose of the study drug.

The primary end points of the trial included complete response (CR) and duration of response (DOR) in those who comprised cohort 1. Key secondary end points comprised time to disease recurrence for patients in cohort 3, as well as time to cystectomy, progression-free survival, event-free survival, and overall survival (OS) for patients across the cohorts examined.

In 89 patients with carcinoma in situ, with or without papillary disease that was refractory or recurred less than 11 months after their last course of BCG, Vicineum produced a CR rate of 40% (95% CI, 33%-51%) at 3 months. At 6 months, 9 months, and 12 months, the CR rates achieved with the agent were 28% (95% CI, 19%-39%), 21% (95% CI, 13%-31%), and 17% (95% CI, 10%-26%), respectively.

Cohort 1 included patients who had carcinoma in situ with or without papillary disease that was refractory or recurred within 6 months of their last course of BCG (n = 82). In these patients, Vicineum induced CR rates of 39%, 26%, 20%, and 17% at 3 months, 6 months, 9 months, and 12 months, respectively.

Patients with carcinoma in situ with or without papillary disease that was refractory or recurred after 6 months, but less than or equal to 11 months, following their last course of BCG comprised cohort 2. At 3 months, the CR rate achieved with Vicineum was 57%; at 6 months, 9 months, and 12 months, these rates were 57%, 43%, and 14%, respectively.

A median DOR of 273 days (95% CI, 122–not applicable [NA]) per the Kaplan-Meier method was observed in those who comprised cohort 1. Moreover, an ad-hoc analysis of pooled data for 93 patients in either cohort 1 or 2 indicated that of those who responded to Vicineum at 3 months, 52% achieved a CR that persisted for 12 months or longer after treatment initiation.

Moreover, patients with high-risk papillary disease experienced higher rates of progressive disease and recurrence. The median time to recurrence in 40 patients who were included in cohort 3 was 402 days (95% CI, 170–NA).

Of all the patients who received treatment with Vicineum (n = 133), more than 75% were estimated to continue to be free of cystectomy at 2.5 years. Data from an ad-hoc analysis that looked at responders vs non-responders showed that 88% of responders were estimated to remain cystectomy free at 3 years. Additionally, 90% of all patients who received Vicineum are estimated to be free of disease progression at 2 years or longer, and 29% were estimated to remain event free at 1 year. Ninety-six percent of patients were estimated to experience an OS of 2 years or longer.

Most adverse effects (AE) reported by patients across the cohorts were low grade. The most common AEs experienced with Vicineum included dysuria (14%), hematuria (13%), and urinary tract infection (12%). Toxicities were noted to be both manageable and reversible.

Only 4 patients discontinued treatment with the product because of AEs. Moreover, 14% of patients experienced serious AEs (SAEs), irrespective of treatment attribution. Four SAEs were reported in 3 patients, and those included grade 3 acute kidney injury, grade 2 pyrexia, grade 4 cholestatic hepatitis, and grade 5 renal failure.

Previously, the biologics license application for Vicineum was granted a priority review from the FDA in February 2021.4


  1. Sesen Bio announces strategic decision to pause clinical development of Vicineum in the US. News release. Sesen Bio. July 18, 2022. Accessed July 18, 2022.
  2. Sesen Bio reports positive, preliminary data update from phase 3 VISTA trial for high-risk non-muscle invasive bladder cancer. News release. Sensen Bio. August 8, 2019. Accessed July 18, 2022.
  3. Vicinium treatment for subjects with non-muscle invasive bladder cancer previously treated with BCG. Updated October 14, 2020. Accessed July 18, 2022.
  4. Sesen Bio announces FDA acceptance and priority review of its biologics license application for Vicineum. News release. Sesen Bio. February 17, 2021. Accessed July 18, 2022.
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