Abstract B58: A phase I/II study of durvalumab and stereotactic radiotherapy in locally advanced pancreatic cancer

Abstract

Abstract Purpose/Objective: Blockade of the PD-1/PD-L1 pathway with radiotherapy (RT) can enhance both local and systemic control in varying tumor types. Yet, no significant responses have been seen in pancreatic cancer (PC). We have previously shown that RT induces PD-1 and PD-L1 in PC following upregulation of interferon-gamma. This mechanism of adaptive immune resistance by PC may serve as an ideal therapeutic target for combined RT and PD-L1 blockade. We report interim results of an ongoing phase 1/2 clinical trial in locally advanced (LA) and borderline resectable (BR) PC (NCT03245541). Materials/Methods: Patients with LA or BR PC treated with standard-of-care gemcitabine and nab-paclitaxel for 3 to 6 cycles were enrolled. Treatment consisted of durvalumab (750 mg Q14 days) on D1. Stereotactic ablative radiotherapy (SABR; 6.6 Gy/fraction) was delivered every other day x 5 fractions beginning D8. Durvalumab continued as maintenance Q14 days until resection or progression. The run-in phase I utilized a standard 3+3 design prior to phase 2 expansion. Dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs) were assessed during the first 10 weeks of study treatment. CT scans were obtained every 2 months for response assessment. Endoscopic research biopsies were obtained pre- and 6-8 weeks post-SABR, and weekly blood samples were obtained on D1, weekly for 10 weeks, and then every 2 months until resection or progression to assess for immune correlates of response. Results: From 8/2017-5/2019, 18 of 30 planned patients were enrolled of whom 13 (72%) were LA and 5 (28%) were BR. Median age was 70 and 44% were female. No DLTs were identified in the phase 1 run in, and enrollment in the phase 2 study continues. Median follow-up from diagnosis is 14 months (range 6-26 months). Median cycles of chemotherapy received prior to enrollment were 4. Grade 3 toxicities have been identified in 2 patients (nausea, anorexia). No patients experienced dose-limiting toxicities. Median PFS was 14 months with median OS not reached. 9 of 18 patients have undergone resection and all were margin negative. BOR: PR (54%); CR (6%), SD (34%), PD (6%). Conclusion: To our knowledge, this is the first report of a PD-L1 inhibitor-RT combination in LA PC. The regimen was safe, well tolerated and appears to be clinically active with high rates of margin-negative resection. Citation Format: Richard Tuli, Nicholas Nissen, Simon Lo, Mourad Tighiouart, Veronica Placencio, Andrew Hendifar. A phase I/II study of durvalumab and stereotactic radiotherapy in locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B58.