Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02.

Abstract

BACKGROUND:

Despite recent changes in the treatment landscape, there remains an unmet need for effective, tolerable, chemotherapy-free treatments for patients with advanced/metastatic urothelial carcinoma (mUC), especially cisplatin-ineligible patients.

OBJECTIVE:

To evaluate the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab in patients with advanced/mUC from the phase 2 multicenter PIVOT-02 study.

DESIGN, SETTING, AND PARTICIPANTS:

This open-label, multicohort phase 1/2 study enrolled patients with previously untreated locally advanced/surgically unresectable or mUC (N = 41).

INTERVENTION:

Patients received BEMPEG 0.006 mg/kg plus nivolumab 360 mg intravenously every 3 wk.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary objectives were safety and the objective response rate (ORR) in patients with measurable disease at baseline and at least one postbaseline tumor response assessment (response-evaluable). Secondary objectives were overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses via univariate logistic regression were performed to test the association between potential biomarkers (CD8+ tumor-infiltrating lymphocytes, tumor mutational burden, and IFN-γ gene expression profile) and response.

RESULTS AND LIMITATIONS:

The ORR was 35% (13/37 evaluable patients) and the complete response rate was 19% (7/37 patients); the median duration of response was not reached. Median PFS was 4.1 mo (95% confidence interval [CI] 2.1-8.7) and median OS was 23.7 mo (95% CI 15.8-not reached). Overall, 40/41 patients (98%) experienced at least one treatment-related adverse event (TRAE); grade 3/4 TRAEs occurred in 11 patients (27%), most commonly pyrexia (4.9%; 2 patients). Exploratory biomarker analyses showed no association between biomarkers and response. Limitations include the small sample size and single-arm design.

CONCLUSIONS:

BEMPEG plus nivolumab was well tolerated and showed antitumor activity as first-line treatment in patients with locally advanced/mUC.

PATIENT SUMMARY:

We investigated an immune-stimulating prodrug called bempegaldesleukin plus the antibody nivolumab as the first therapy for patients with advanced or metastatic cancer of the urinary tract. This combination had manageable treatment-related side effects and was effective in a subset of patients. This trial is registered at ClinicalTrials.gov as NCT02983045.

• Authors: Arlene O Siefker-Radtke, Daniel C Cho, Adi Diab, Mario Sznol, Mehmet A Bilen, Arjun V Balar, Giovanni Grignani, Erika Puente, Lily Tang, David Chien, Ute Hoch, Arkopal Choudhury, Danni Yu, Sue L Currie, Mary A Tagliaferri, Jonathan Zalevsky, Michael E Hurwitz, Nizar M Tannir
• Journal: European urology (Eur Urol) Vol. 82 Issue 4 Pg. 365-373 (10 2022) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 35643589 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-2
• Prodrugs
• Nivolumab

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Carcinoma, Transitional Cell (drug therapy, secondary)
• Humans
• Interleukin-2 (therapeutic use)
• Nivolumab (adverse effects)
• Prodrugs (therapeutic use)
• Urinary Bladder Neoplasms (drug therapy, etiology)