A phase Ib trial of neoadjuvant/adjuvant durvalumab +/- tremelimumab in locally advanced renal cell carcinoma (RCC).
Moshe Chaim Ornstein, Joseph Zabell, Laura S. Wood, Brian P. Hobbs, Sarah Devonshire, Allison Martin, Kimberly D Allman, Arpit Rao, Timothy D. Gilligan, Steven C. Campbell, Venkatesh Krishnamurthi, Brian I. Rini
Abstract
5021 Background: Effective neoadjuvant and adjuvant therapies are lacking in locally advanced RCC. Given robust activity of checkpoint inhibitors in mRCC, a phase Ib trial of perioperative Durvalumab (D) +/- Tremelimumab (T) in locally advanced RCC was conducted (NCT02762006). Methods: Pts with radiographic evidence of high risk localized RCC (clinical stage T2b-4 and/or N1, M0 disease), adequate performance status, and adequate laboratory values were eligible. Primary objective was safety and feasibility of neoadjuvant/adjuvant D +/- T. Results: Twenty-nine pts were enrolled. Cohorts, regimens, and immune-related adverse events (irAE) are detailed in the table. In total, 79% male, median age 61 (range, 42-84), 8%/88%/4% clinical T2/T3/T4, 27% positive clinical lymph nodes (LN+), and median time from neoadjuvant dose to surgery was 7 days. On surgical pathology: 5%/14%/77%/5% pathologic T1/T2/T3/T4, and 13% LN+. Median time from treatment to first grade (Gr) >3 irAE or any Gr irAE requiring corticosteroids was 99 days (range, 32-207). There were no treatment-related delays to nephrectomy or surgical complications. Although not meeting the protocol-defined MTD, given higher than expected irAEs, the study was suspended. Conclusions: Perioperative durvalumab in locally advanced RCC appears safe. The addition of tremelimumab is associated with higher rates of toxicity. Updated toxicity will be presented. Clinical trial information: NCT02762006 . [Table: see text]