Phase I/II open-label trial to evaluate the safety and preliminary efficacy of <sup>177</sup>Lu-OPS201, a radiolabeled somatostatin receptor antagonist, in patients with somatostatin receptor-positive, progressive gastroenteropancreatic neuroendocrine tumors — ASN Events
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  3. Phase I/II open-label trial to evaluate the safety and preliminary efficacy of 177Lu-OPS201, a radiolabeled somatostatin receptor antagonist, in patients with somatostatin receptor-positive, progressive gastroenteropancreatic neuroendocrine tumors

Phase I/II open-label trial to evaluate the safety and preliminary efficacy of 177Lu-OPS201, a radiolabeled somatostatin receptor antagonist, in patients with somatostatin receptor-positive, progressive gastroenteropancreatic neuroendocrine tumors (#57)

Guillaume Nicolas 1 2 , Richard Baum 3 , Ken Herrmann 4 5 , Michael Lassmann 4 , Rod Hicks 6 , Alexander Haug 7 , Heike Oberwittler 8 , Hakim Bouterfa 9 , Damian Wild 1 10
  1. Dept of Radiology, Division of Nuclear Medicine, University of Basel, Basel, Switzerland
  2. Neuroendocrine Tumour Unit, Royal Free Hospital, London, Berks, United Kingdom
  3. THERANOSTICS Center for Molecular Radiotherapy & Molecular Imaging, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany
  4. Dept of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
  5. Dept of Molecular & Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, USA
  6. Centre for Cancer Imaging, Molecular Imaging & Targeted Therapeutics Laboratory, The Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  7. Division of Nuclear Medicine, Dept of Biomedical Imaging & Image-Guided Therapy, University of Vienna, Vienna, Austria
  8. Ipsen, Les Ulis, France
  9. Octreopharm, Ipsen, Berlin, Germany
  10. Center of Neuroendocrine & Endocrine Tumors, University of Basel Hospital, Basel, Switzerland

Background: Approximately 80% of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) express somatostatin receptors (SSTRs); consequently, radiolabeled somatostatin analogues have become an integral part of their diagnosis and treatment. The latter (peptide receptor radionuclide therapy [PRRT]) is highly effective as it delivers targeted radiation to the tumour cells. Currently, SSTR agonists are used for PRRT. Preclinical and preliminary clinical data have indicated that tumour uptake and tumour-to-tissue radionuclide uptake ratio are higher with radiolabeled SSTR antagonists than agonists. DOTA-JR11 (OPS201) is a next-generation SSTR antagonist, which is selective for SSTR2, one of the most commonly expressed SSTR subtypes on GEP‑NETs. 

Methods: This is a Phase I/II, international, multicenter, open-label study evaluating 177Lu-OPS201 as PPRT for GEP‑NETs (NCT02592707; EudraCT 2015-002867-41). It is planned to enroll 45 patients ≥18 years old with unresectable, SSTR-positive, progressive GEP-NETs (RECIST1.1). During Phase A, patients (n=15) receive three cycles of 177Lu‑OPS201 treatment, at an activity of 5.5 GBq every 8 weeks; the activities in cycles 2 and 3 may be lowered (or omitted) depending on the cumulative organ doses in the kidney and bone marrow, and their toxicities. In Phase B, patients (n=30) receive three cycles of 177Lu‑OPS201 at activities up to 7.4 GBq, depending on the results of Phase A. At the end of Phase B, patients will be followed-up every 3 months for 2 years. The primary endpoint is safety; secondary endpoints include: 177Lu-OPS201 pharmacokinetics and biodistribution (maximal uptake and time-integrated activity coefficient in target lesion, discernible organs and blood); radiation dosimetry (organ and tumour doses); and preliminary efficacy (tumour response [RECIST1.1], progression-free survival during long-term follow-up), and quality-of-life. This study will evaluate the safety and efficacy of a whole PRRT treatment using 177Lu-OPS201. The first patient to be recruited is expected in July 2016.