Phase I study of the 177 Lu-DOTA 0-Tyr 3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung

J Immunother Cancer. 2020 Jul;8(2):e000980. doi: 10.1136/jitc-2020-000980.


Background: Lutathera is a 177Lutetium-labeled somatostatin analog approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Somatostatin receptors are expressed in small cell lung cancer (SCLC). Nivolumab, an anti-PD-1 antibody, may act synergistically with lutathera to generate antitumor immunity. We conducted a phase I study of lutathera plus nivolumab in patients with advanced NETs of the lung.

Methods: Patients with relapsed/refractory extensive-stage SCLC (ES-SCLC), non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).

Results: Nine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.

Conclusions: Lutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.

Trial registration number: NCT03325816.

Keywords: drug therapy, combination; immunotherapy; lung neoplasms; radioimmunotherapy.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / drug therapy*
  • Nivolumab / pharmacology
  • Nivolumab / therapeutic use*
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacology
  • Octreotide / therapeutic use
  • Organometallic Compounds / pharmacology
  • Organometallic Compounds / therapeutic use*


  • Organometallic Compounds
  • Nivolumab
  • lutetium Lu 177 dotatate
  • Octreotide

Associated data