{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:29:50Z","timestamp":1792546190202,"version":"4.5.0"},"reference-count":24,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"unspecified","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018720","name":"Advanced Accelerator Applications","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018720","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,6,2]]},"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Lutathera is a <jats:sup>177<\/jats:sup>Lutetium-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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2009mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240\u2009mg every 2 weeks).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Lutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial results\" xlink:href=\"NCT03325816\">NCT03325816<\/jats:ext-link>\n                  <\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-000980","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T02:05:37Z","timestamp":1593741937000},"page":"e000980","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":91,"title":["Phase I study of the <sup>177<\/sup>Lu-DOTA<sup>0<\/sup>-Tyr<sup>3<\/sup>-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct03325816","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-8684","authenticated-orcid":false,"given":"Chul","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4852-3914","authenticated-orcid":false,"given":"Stephen V","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa S","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tisdrey","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Loda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Weill Medical College of Cornell University, New York, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Radiology, Georgetown University, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Giaccone","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA"},{"name":"Division of Hematology and Oncology, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"2025100312404140000_8.2.e000980.1","unstructured":"Howlader NNA , Krapcho M , Garshell J , et al . 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