{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:14:07Z","timestamp":1788506047599,"version":"build-2803163510"},"reference-count":31,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Delta-Fly Pharma, Inc."}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aminopeptidase N (CD13) has been reported to be a prognostic factor in non-small cell lung cancer (NSCLC). DFP-14323 (INN: ubenimex) is a CD13 inhibitor and a low-toxicity, non-specific immunomodulator approved in Japan for the maintenance treatment of adult acute non-lymphocytic leukemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study explored the potential immunomodulatory synergy of DFP-14323 with EGFR-TKIs in patients with advanced NSCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A prospective, multicenter, open-label, single-arm phase II study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Stage III\/IV treatment-na\u00efve patients with activating\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      mutation-positive (Ex19del\/L858R) NSCLC were treated with 10 mg\/day of DFP-14323 and a starting dose of 20 mg\/day of afatinib, continued until disease progression or intolerable toxicity. The primary endpoint was the disease control rate (DCR). A total of 26 patients were enrolled based on Simon\u2019s two-stage design (threshold DCR of 70%, expected DCR of 90%; two-sided \u03b1=0.05, \u03b2 error=0.20).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The DCR as primary endpoint was 100% (95% confidence interval (CI), 86.8\u2013100.0%). Independent radiological review at 72 weeks demonstrated a median progression-free survival (PFS) of 16.6 months (95% CI, 10.2\u201322.9). Updated investigator-exploratory follow-up revealed a median PFS was 23.1 months (95% CI, 12.9\u2013 not estimable; median follow-up period: 22.6 months). One grade 3 paronychia was considered DFP-14323-related, while other adverse events were attributable to afatinib. No grade 4-5 adverse events occurred. Grade 1 interstitial lung disease occurred in one patient and resolved quickly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The combination of DFP-14323 and low-dose afatinib was considered to have the potential for future clinical utility for\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      mutation-positive NSCLC. As the next step, a study evaluating this combination therapy in uncommon\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      mutation-positive NSCLC is currently underway in Japan (jRCT2061230111).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261483551","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:04:00Z","timestamp":1788293040000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase II study of DFP-14323, a non-specific immunomodulator, in combination with low-dose afatinib as first-line therapy for common\n                    <i>EGFR<\/i>\n                    mutation-positive NSCLC"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-0481","authenticated-orcid":false,"given":"Hiroshige","family":"Yoshioka","sequence":"first","affiliation":[{"name":"Kansai Medical University Hospital"},{"name":"Dokkyo Medical University Saitama Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Mori","sequence":"additional","affiliation":[{"name":"National Hospital Organization Osaka Toneyama Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Katakami","sequence":"additional","affiliation":[{"name":"Takarazuka City Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Kurashiki Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Osaka Metropolitan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Hyogo Prefectural Amagasaki General Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Tamiya","sequence":"additional","affiliation":[{"name":"Osaka International Cancer Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Yokohama City University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-long","family":"Huang","sequence":"additional","affiliation":[{"name":"Kitano Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.29.97"},{"key":"e_1_3_8_3_2","first-page":"2971","article-title":"Toxicological studies on bestatin. 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