Abstract CT164: A Phase II clinical trial of GVAX pancreas vaccine (with Cyclophosphamide) in combination with Nivolumab and Stereotactic Body Radiation Therapy (SBRT) followed by definitive resection for patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC)
Authors: Osipov Arsen , Sugar Elizabeth , Ferguson Anna , Durham Jennifer , Rodriguez Christina , Parkinson Rose , Sena Laura , Zheng Lei , Wolfgang Christopher , Burkhart Richard , He Jin , Weiss Matthew , Narang Amol , Laheru Daniel , Azad Nilofer , Jaffee Elizabeth , Weekes Colin , Yarchoan Mark 
Published: August 2019

Abstract
Background: A strong rationale exists for the use of preoperative therapy in BR-PDAC, because upfront surgery in these patients results in a high probability of incomplete resection. Recently, the Alliance A021101 trial, which utilized neoadjuvant FOLFIRINOX and chemoradiation, demonstrated the safety and clinical activity of neoadjuvant therapy in BR-PDAC. The present clinical trial will evaluate the safety and clinical activity of neoadjuvant Stereotactic Body Radiation Therapy (SBRT) in combination with neoadjuvant cyclophosphamide (Cy)/GVAX pancreas vaccine/nivolumab immunotherapy after completion of standard chemotherapy in patients with BR- PDAC. GVAX is an allogeneic, whole-cell, GM-CSF-secreting vaccine that induces T-cell immunity against tumor-associated antigens. GVAX has previously been studied in combination with low-dose Cy to inhibit regulatory T cells. In prior studies, neoadjuvant Cy/GVAX induced high levels of PD-L1 expression and the formation of novel vaccine-induced, immunologically active, tertiary lymphoid aggregates. Methods: In this multi-center, open label, phase II clinical trial, patients with BR-PDAC will receive a total of four 28-day cycles of FOLFIRINOX. Subsequently they will undergo EUS-guided fiducial placement along with SBRT simulation and core biopsy. Within 2-6 weeks after chemotherapy, patients will receive their first dose of combination immunotherapy, consisting of Cy 200 mg/m2 IV and nivolumab 240mg IV on day 1 followed by 5 x 108 GVAX vaccine cells, administered as six intradermal injections, on day 2. Approximately three weeks later, patients will receive their second dose of combined immunotherapy on the same day as initiation of SBRT (6.6 Gy x 5 days). Following completion of immunotherapy and SBRT, patients will undergo repeat imaging, surgical re-evaluation and if resectable, proceed to definitive surgical resection. This study will recruit 50 patients to achieve 45 evaluable patients receiving immunotherapy. The primary endpoint is pCR rate. Secondary endpoints include: rate of R0 resections, ORR, OS, distant metastasis free survival, adverse events (graded by NCI CTCAE). Additionally, exploratory objectives include evaluating: 1. intratumoral immune infiltrates in pre- and post-treatment biopsy specimens utilizing immunohistochemistry and transcriptional analysis, 2. circulating biomarkers including plasma tumor DNA and circulating tumor cells. Key inclusion criteria for this study include: having BR- PDAC, no more than 1 month or 1 cycle (28 days) of systemic therapy for PDAC, and ECOG performance status of ≤ 1. This clinical trial is open, actively recruiting and is supported by BMS and the Skip Viragh Foundation. Clinical trial information: NCT03161379.
Citation Format: Arsen Osipov, Elizabeth Sugar, Anna Ferguson, Jennifer Durham, Christina Rodriguez, Rose Parkinson, Laura Sena, Lei Zheng, Christopher Wolfgang, Richard Burkhart, Jin He, Matthew Weiss, Amol Narang, Daniel Laheru, Nilofer Azad, Elizabeth Jaffee, Colin Weekes, Mark Yarchoan. A Phase II clinical trial of GVAX pancreas vaccine (with Cyclophosphamide) in combination with Nivolumab and Stereotactic Body Radiation Therapy (SBRT) followed by definitive resection for patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT164.