AUA 2021: Interim Analysis of a Phase I Single-Arm Study of the Combination of Durvalumab and Vicineum in Subjects with High-Grade NMIBC Previously Treated with BCG 

( At the 2021 American Urologic Association (AUA) annual meeting, the bladder cancer non-invasive session included a presentation by Dr. Sandeep Gurram discussing interim results of a phase 1 trial combining durvalumab and Vicineum in patients with high-grade non-muscle invasive bladder cancer (NMIBC) previously treated with bacillus calmette–guérin (BCG) intravesical therapy. Indeed, radical cystectomy is the gold standard treatment for high-risk NMIBC that fails to respond to intravesical treatment with BCG. However, some patients are unfit or refuse radical cystectomy due to the relatively high complication rates and significant changes in the patient's lifestyle. Therefore, there is a large unmet need in therapeutic options for NMIBC that recurs or progresses. Vicineum is a recombinant fusion protein comprised of an anti-EpCAM linked to a truncated form of Pseudomonas exotoxin A; of note, 98% of BCG-refractory patients have EpCAM overexpression. Previously the phase III VISTA trial demonstrated efficacy in the BCG failure population with a duration of response in patients with a complete response of 287 days. Dr. Gurram and colleagues presented interim results from the first 12 patients treated thus far with a combination of Vicineum and durvalumab in BCG-unresponsive NMIBC.

This is a single institution, phase I study with an estimated accrual of 24 patients, of which 12 patients who met the inclusion criteria and were enrolled were analyzed.  The primary objective was to evaluate the safety and tolerability of durvalumab and Vicineum in combination in subjects with BCG-unresponsive high-grade NMIBC who have failed appropriate BCG therapy and who elected not to undergo radical cystectomy or were considered unfit. Twelve-week response was evaluated by cytology and mandatory biopsy. Secondary objectives included biomarker analysis of response including urinary EpCAM and PD-L1/PD-1 expression. Recurrence free survival and treatment related adverse events were also recorded. The study design for this phase 1 trial is as follows:

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Among the 12 patients enrolled, 11 (92%) were male, the median age at enrollment was 69.5 years (range 57-82), two patients had T1 disease (17%), six patients had high-grade Ta (50%), and four patients had CIS + papillary tumor (33%). The median number of BCG induction courses was 2 (range 1-4). The safety cohort was a 3+3 design with all six subjects enrolled without any dose related toxicities. The maximum tolerated dose was determined to be 30 mg Vicineum in 50 mL of saline. All 12 patients showed at least one treatment related adverse event but only 8% were grade 3 or higher. The most common adverse event has been urinary frequency (5/12, 41%):

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Five patients (42%) were disease free at first 12-week evaluation, 4/12 (33%) at 6 months, and 2/12 (17%) at the 12-month evaluation:

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On biomarker analysis, a decrease in urinary EpCAM and a 5-10 fold increase in PD-L1 at week 3-5 were observed.

Dr. Gurram concluded his presentation of the interim results of this phase 1 trial combining durvalumab with Vicineum in BCG unresponsive NMIBC with the following concluding statements:

  • The combination of Vicinium and durvalumab in BCG unresponsive NMIBC is safe and well-tolerated with no new safety signals
  • The doublet has a similar safety profile compared to both agents used individually
  • The interim analysis shows a 12-week response rate of 42%, with a prolonged (>12mo) effect in some patients
  • Further biomarker analysis may be helpful in predicting responders

Presented by: Sandeep Gurram M.D, National Institutes of Health - Urologic Oncology Branch, Bethesda, MD

Co-Authors: Sonia Bellfield R.N, Ms.N, Rebecca Dolan N.P, Beatriz Walter M.D, Ph.D, Maria Merino M.D, Scot Niglio M.D, Andrea Apolo M.D, Piyush Agarwal M.D, Vladimir Valera M.D, Ph.D

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.

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