FDA Issues Complete Response Letter to Bladder Cancer Treatment BLA

Approval sought for oportuzumab monatox-qqrs (Vicinium) for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), which was previously granted priority review by the FDA.

The FDA issued a complete response letter (CRL) to Sesen Bio for its Biologics License Application (BLA) for oportuzumab monatox-qqrs (Vicinium) for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC),1 which was previously granted priority review.2

The approval was denied pending additional clinical and statistical data and analyses requested by the FDA to potentially approve oportuzumab monatox-qqrs for this indication at a later date. In the CRL, the FDA stated that Chemistry, Manufacturing and Controls issues still must be addressed.

“We are deeply disappointed by this unexpected result, and it is an unfortunate day for patients suffering from BCG-unresponsive NMIBC,” said Thomas Cannell, president, and chief executive officer of Sesen Bio, in a press release. “We remain dedicated to our mission to save and improve the lives of patients by bringing new treatment options to patients, and we intend to work closely with the FDA to understand next steps.”

Oportuzumab monatox-qqrs, a recombinant fusion protein that blocks protein synthesis to mediate tumor cell death, is currently being investigated across several solid tumor types.

The drug was evaluated in phase 3 study with an estimated enrollment of 134 patients and a primary outcome of complete response rate up to 24 months. Secondary outcome measures include recurrence rate, event-free survival, number of patients with adverse events as a measure of tolerability, changes in echocardiogram, changes in vital signs from baseline, changes in laboratory or physical examination, complete response rate, time to cystectomy, time to disease recurrence, time to progression, progression-free survival, and overall survival (OS).1,3

During the single-arm study, patients received 30 mg of oportuzumab monatox-qqrs in 50 ml of saline, twice weekly for 6 weeks followed by once weekly for 6 weeks. After the 12-week induction period, patients were administered maintenance oportuzumab monatox-qqrs in 50 ml of saline administered once weekly every other week up to 104 weeks.3

The results showed a 3-month complete response rate of 40% and a median DoR of 9.4 months (95% CI, 5.1 to not evaluable [NE]). Among patients who responded, 52% remained disease-free for a year after treatment initiation. The 2-year OS rate was (96% 95% CI, 92%-100%).

The majority of adverse events (AEs) observed were grades 1 and 2. Severe AEs included grade 4 cholestatic hepatitis, grade 5 renal failure, grade 3 acute kidney injury, and grade 2 pyrexia. Three percent of patients discontinued treatment due to AEs.

A phase 3 follow-up trial, VISTA study (NCT02449239), of the trial is currently underway to further investigate the efficacy and safety of NCT02449239. A Type A meeting with the FDA will be requested by Sesen Bio, the company announced, to discuss the steps needed to obtain FDA-approval for oportuzumab monatox-qqrs for the treatment of BCG-unresponsive NMIBC.1


1. Sesen Bio receives complete response letter from fda for Vicineum™ (oportuzumab monatox-qqrs). News release. Sesen Bio. August 13. 2021. Accessed August 16, 2021. https://bit.ly/3xQdt1e

2. Sesen Bio Announces FDA Acceptance and Priority Review of its Biologics License Application for Vicineum™. News release. Sesen Bio. February 16, 2021. Accessed February 17, 2021. https://bit.ly/37pBstN

3. Shore N, O’Donnell M, Keane T, et al. PD03-02 Phase 3 results of Vicinium in bcg-unresponsive non-muscle invasive bladder cancer. J Urol. 2020; 203(suppl 4). doi: 10.1097/JU.0000000000000823.02