MP16-20: Final Results of a Phase I, Single-Arm Clinical Trial of the Combination of Durvalumab and Vicineum in BCG Unresponsive, High-Risk Non-Muscle-Invasive Bladder Cancer Patients (NCT03258593)
Friday, May 3, 2024 1:00 PM to 3:00 PM · 2 hr. (US/Central)
221B
Abstract
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Full Abstract and Figures
Author Block
Genesis Rivera-Marquez, Beatriz Walter, Rebecca Dolan, Sonia Belfield, Maria Merino, Sandeep Gurram, Andrea Apolo, Scot Niglio, Bethesda, MD, Piyush Agarwal, Chicago, IL, Vladimir A. Valera*, Bethesda, MD
Introduction
Radical cystectomy remains the gold standard for the treatment of high-risk, non-muscle invasive bladder cancer (NMIBC) that fails to respond to intravesical treatment with BCG. Some patients are unfit or refuse this therapeutic option. Therefore, there is an unmet clinical need for alternative treatments in this population. The combination of new and alternative intravesical therapies with or without systemic agents has emerged as the new treatment paradigm. In this study, we aimed to evaluate the safety and tolerability of clinical trial that combined Vicineum and Durvalumab in BCG-unresponsive NMIBC.
Methods
Data from a single institution, phase I study using a combined regimen that included the intravesical administration of a fusion protein containing an antibody fragment against EpCAM linked to a truncated Pseudomonas Exotoxin A (Oportuzumab Monatox, Vicineum) together with the systemic PDL-1 inhibitor Durvalumab was evaluated. Twelve-week response was evaluated by cytology and mandatory biopsy. Treatment related adverse events (TrAE) were recorded as primary objective (safety and tolerability). Secondary objectives included correlatives analysis of response such as urinary EpCAM, PD-L1/PD-1, plasma cytokine expression, as well as recurrence-free survival.
Results
Fifteen patients were ultimately enrolled from an expected 24 patient accrual. Ninety-three per cent were male. Mean age at enrollment was 72 years (range 52-83 years). Seven patients (47 %) had HG Ta disease, 20% were HG T1 (3/15) and 5 (33%) had Tis at enrollment. Seven patients (47%) were disease free at first 12-week evaluation and 6/15 (40%) at 6 months. Of these, three patients have remained with no evidence of disease for >12 months. All 15 patients showed at least 1 treatment related adverse event and 27% were grade 3 or higher. The most common adverse events were related to voiding symptoms and hematuria. On biomarker analysis, a decrease in urinary EpCAM and a 5-10 fold increase in PD-L1 at week 3-5 was observed. Median recurrence-free survival was 13.2 months (12.28- NR).
Conclusions
The combination of Vicineum and Durvalumab was safe and well tolerated and had a 12-week response rate of almost 50%, with a prolonged (>12mo) benefit in some patients with high risk NMIBC who have failed BCG treatment.
Source Of Funding
NIH Intramural Cancer Research Program
Author Block
Genesis Rivera-Marquez, Beatriz Walter, Rebecca Dolan, Sonia Belfield, Maria Merino, Sandeep Gurram, Andrea Apolo, Scot Niglio, Bethesda, MD, Piyush Agarwal, Chicago, IL, Vladimir A. Valera*, Bethesda, MD
Introduction
Radical cystectomy remains the gold standard for the treatment of high-risk, non-muscle invasive bladder cancer (NMIBC) that fails to respond to intravesical treatment with BCG. Some patients are unfit or refuse this therapeutic option. Therefore, there is an unmet clinical need for alternative treatments in this population. The combination of new and alternative intravesical therapies with or without systemic agents has emerged as the new treatment paradigm. In this study, we aimed to evaluate the safety and tolerability of clinical trial that combined Vicineum and Durvalumab in BCG-unresponsive NMIBC.
Methods
Data from a single institution, phase I study using a combined regimen that included the intravesical administration of a fusion protein containing an antibody fragment against EpCAM linked to a truncated Pseudomonas Exotoxin A (Oportuzumab Monatox, Vicineum) together with the systemic PDL-1 inhibitor Durvalumab was evaluated. Twelve-week response was evaluated by cytology and mandatory biopsy. Treatment related adverse events (TrAE) were recorded as primary objective (safety and tolerability). Secondary objectives included correlatives analysis of response such as urinary EpCAM, PD-L1/PD-1, plasma cytokine expression, as well as recurrence-free survival.
Results
Fifteen patients were ultimately enrolled from an expected 24 patient accrual. Ninety-three per cent were male. Mean age at enrollment was 72 years (range 52-83 years). Seven patients (47 %) had HG Ta disease, 20% were HG T1 (3/15) and 5 (33%) had Tis at enrollment. Seven patients (47%) were disease free at first 12-week evaluation and 6/15 (40%) at 6 months. Of these, three patients have remained with no evidence of disease for >12 months. All 15 patients showed at least 1 treatment related adverse event and 27% were grade 3 or higher. The most common adverse events were related to voiding symptoms and hematuria. On biomarker analysis, a decrease in urinary EpCAM and a 5-10 fold increase in PD-L1 at week 3-5 was observed. Median recurrence-free survival was 13.2 months (12.28- NR).
Conclusions
The combination of Vicineum and Durvalumab was safe and well tolerated and had a 12-week response rate of almost 50%, with a prolonged (>12mo) benefit in some patients with high risk NMIBC who have failed BCG treatment.
Source Of Funding
NIH Intramural Cancer Research Program