Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ili
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ORIGINAL ARTICLE
Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors Robin Fröbom1,2 · Erik Berglund3,4 · David Berglund5 · Inga‑Lena Nilsson1,2 · Jan Åhlén1,2 · Karin von Sivers6 · Christina Linder‑Stragliotto2 · Peter Suenaert7 · Alex Karlsson‑Parra5,7 · Robert Bränström1,2 Received: 23 February 2020 / Accepted: 28 May 2020 © The Author(s) 2020
Abstract Background The majority of patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib, and subsequent treatments have limited efficacy. Ilixadencel (allogeneic inflammatory dendritic cells) is a cell-based immune primer injected intratumorally that previously has been clinically investigated in metastatic renal cell carcinoma and hepatocellular carcinoma. Methods The trial was a single arm phase I trial assessing safety and efficacy of ilixadencel in subjects with progressing advanced/metastatic GIST despite ongoing treatment with second or later lines of tyrosine kinase inhibitors (TKI). Three patients were progressing while on sunitinib (second line), one on regorafenib (third line), and two on pazopanib (fourth line). TKI treatment was maintained throughout, while two intratumoral injections of ilixadencel (10 × 106 viable and HLADR expressing cells per dose) were administered. Results No severe adverse events were found to be related to ilixadencel administration. Four patients showed continued tumor progression at 3 months per RECIST 1.1 and Choi criteria. One patient (on third line regorafenib) had stable disease for 9 months and another patient (on second line sunitinib) had stable disease at end of study (12 months) as per RECIST 1.1. These two patients developed a partial response as per Choi criteria with a duration of 3 and 6 months, respectively. The median progression-free survival (PFS) was 4.0 months. Conclusion Ilixadencel treatment presented an acceptable safety profile among advanced GIST patients who developed resistance to TKI. Encouraging radiological tumor responses were detected in 33% of treated patients, supporting further investigation. Clinical trial registration www.clinicaltrials.gov; NCT: 02432846; registration date: February 22, 2016. Keywords Gastrointestinal stromal tumor · Immunotherapy · Cell therapy · Ilixadencel · Tyrosine kinase inhibitor · Dendritic cells
Introduction
Robin Fröbom and Erik Berglund shared authorship. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02625-5) contains supplementary material, which is available to authorized users. * Erik Berglund [email protected] Extended author information available on the last page of the article
Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract, most frequently located in the stomach or small intestine. About 85–90% of GIST possess a gain-of-function mutation in the KIT or PDGFRA gene [1]. Two decades a
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