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BackgroundEpithelioid hemangioendothelioma is a rare vascular tumor of borderline or low-grade malignancy. The lungs and liver are the two common primary organs affected. Metastatic disease was reported in more than 100 cases in the literature. However, no firm conclusions can be determined for recommended treatment options.Case presentationThe current case presents a patient with metastatic pulmonary epithelioid hemangioendothelioma to the cervical and mediastinal lymph nodes, lungs and liver that has been treated with pazopanib for more than two years with PET avid complete metabolic response in the mediastinum and lungs, and long-lasting stable disease. Target therapies that block VEGFR have a logical base in this rare malignancy.ConclusionsThe current case is the first to report objective, long-lasting response to pazopanib.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is largely unresponsive to checkpoint inhibitors. Blockade of the CXCR4/CXCL12 axis increases intratumoral trafficking of activated T cells while restraining immunosuppressive elements. This study evaluates dual blockade of CXCR4 and PD1 with chemotherapy in PDAC. Patients and Methods: Multicenter, single-arm, phase II study to evaluate the safety and efficacy of motixafortide and pembrolizumab combined with chemotherapy in patients with de novo metastatic PDAC and disease progression on front-line gemcitabine-based therapy (NCT02826486). Subjects received a priming phase of motixafortide daily on days 1–5, followed by repeated cycles of motixafortide twice a week; pembrolizumab every 3 weeks; and nanoliposomal irinotecan, fluorouracil, and leucovorin every 2 weeks (NAPOLI-1 regimen). The primary objective was objective response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), safety, and tolerability. Results: A total of 43 patients were enrolled. The ORR according to RECISTv1.1 was 21.1% with confirmed ORR of 13.2%. The DCR was 63.2% with median duration of clinical benefit of 5.7 months. In the intention-to-treat population, median PFS was 3.8 months and median OS was 6.6 months. The triple combination was safe and well tolerated, with toxicity comparable with the NAPOLI-1 regimen. Notably, the incidence of grade 3 or higher neutropenia and infection was 7%, lower than expected for this chemotherapy regimen. Conclusions: Triple combination of motixafortide, pembrolizumab, and chemotherapy was safe and well tolerated, and showed signs of efficacy in a population with poor prognosis and aggressive disease.

TPS4672 Background: KRAS alterations are the most frequent driver alterations identified in pancreas cancer; however, KRAS has remained an elusive therapeutic target. siG12D-LODER is a novel, miniature bio-degradable polymeric matrix encompassing a novel small interfering RNA targeting KRAS G12D and all additional G12X mutations (G12C, G12V...). The siG12D-LODER is inserted directly into the pancreas tumor via endoscopic intervention. A Phase 1/2a dose escalation and expansion study of patients receiving a one-time dose of siG12D-LODER with ongoing chemotherapy demonstrated that the combination was well-tolerated and safe and exhibited promising potential efficacy with 10/12 patients achieving disease control and median overall survival 15.1 months (Golan, Oncotarget 2015). Methods: This phase 2 study was initially designed as a randomized, two arm, open label study of gemcitabine and nab-paclitaxel with or without siG12D-LODER for patients with locally advanced pancreas cancer with planned 40 patients in each arm and primary endpoint of progression-free survival. Eighteen patients were enrolled in the chemotherapy alone arm and 18 in the chemotherapy and siG12D-LODER arm. After an interim analysis, the study design has been amended and is now a single arm study in which patients (N=39) with both borderline resectable and locally advanced pancreas cancer will receive investigator’s choice of chemotherapy (the combination of gemcitabine/nab-paclitaxel or modified FOLFIRINOX) and all patients will receive up to three doses of the siG12D-LODER administered once every 12 weeks. Primary endpoint is overall response rate after final siG12D-LODER insertion. Secondary endpoints include duration of response, progression-free survival, overall survival, time to response, percentage of patients proceeding to surgical resection, and percentage of patients receiving radiation therapy. Exploratory analyses include evaluation of KRAS mutation status and monitoring of circulating free DNA and circulating tumor cells. The amended protocol is now open for accrual and four patients having been enrolled to date. Trial accrual is anticipated to be completed by December 2020. Clinical trial information: NCT01676259 .