ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 52 P36 | DOI: 10.1530/endoabs.52.P36

Phase 1/2 open-label trial to assess the safety and preliminary efficacy of 177Lu-OPS201 as peptide receptor radionuclide therapy in patients with somatostatin receptor-positive, progressive neuroendocrine tumours

Guillaume Nicolas1,2, Richard Baum3, Ken Herrmann4,5, Michael Lassmann4, Rodney Hicks6, Alexander Haug7, Shaunak Navalkissoor2, Heike Oberwittler8, Tiffany Wang9 & Damian Wild1

1University of Basel Hospital, Basel, Switzerland; 2Royal Free Hospital, London, UK; 3Zentralklinik Bad Berka, Bad Berka, Germany; 4University Hospital Würzburg, Würzburg, Germany; 5UCLA, Los Angeles, California, USA; 6Peter MacCallum Cancer Centre, East Melbourne, Australia; 7Medical University of Vienna, Vienna, Austria; 8Ipsen, Les Ulis, France; 9Ipsen, Cambridge, Massachusetts, USA.

Introduction: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin receptor (SSTR) agonists is highly effective and has become an integral part of neuroendocrine tumour (NET) treatment. However, tumour uptake and tumour-to-tissue dose ratios may be higher with radiolabelled SSTR antagonists than agonists. OPS201 (DOTA-JR11) is a very promising next-generation SSTR antagonist selective for SSTR2 (expressed by NETs). This phase 1/2, international, single-arm, open-label study will evaluate 177Lu-OPS201 as PRRT in 45 adults with unresectable, SSTR-positive, progressive gastroenteropancreatic (GEP)-NETs, lung NETs, phaeochromocytomas and paragangliomas.

Subjects & methods: Patients are recruited at 15 study centres in Australia, Europe, and the US with experience in the use of PRRT (or other radionuclide therapy). The core trial comprises phases A and B. Phase A: six patients receive three cycles of 177Lu-OPS201 at 4.5 GBq over 24 weeks; a further nine patients receive three cycles of 177Lu-OPS201 at 4.5 GBq, or an activity not evoking dose-limiting toxicity, dependent on initial safety/dosimetry data. Phase B: 30 patients receive three cycles of 177Lu-OPS201 at up to 7.4 GBq, dependent on phase-A safety/dosimetry data. In a subsequent long-term follow-up, tumour response (centrally reviewed [RECIST v1.1]) will be assessed using computed tomography/magnetic resonance imaging every 3 months from the end-of-core-trial visit for 2 years, or until progressive disease/death. This core study and long-term follow-up are together expected to last 42–45 months.

Results: The primary endpoint is safety and tolerability (based on physical examination, vital signs, electrocardiogram, clinical laboratory measurements, adverse events, dose-limiting toxicities, concomitant medication, pituitary markers and bone marrow aspirate in case of persisting toxicities of grade 3 or more). Secondary endpoints include: biodistribution and pharmacokinetics (maximal uptake, area-under-curve, terminal half-life); radiation dosimetry; preliminary efficacy (tumour response, progression-free survival), and quality of life. Treatment in phase A is underway.

Conclusions: This study will provide important information regarding the safety and efficacy of the radiolabelled SSTR antagonist 177Lu-OPS201 as PRRT in patients with SSTR-positive, progressive GEP-NETs, lung NETs, phaeochromocytomas and paragangliomas (EudraCT 2015-002867-41; NCT02592707).