{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:20:38Z","timestamp":1791822038314,"version":"4.3.4"},"reference-count":40,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"32","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2019,11,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Metastatic mucosal melanoma responds poorly to anti\u2013programmed cell death-1 (PD-1) monotherapy. Vascular endothelial growth factor (VEGF) has been shown to play an important immunosuppressive role in the tumor microenvironment. The combination of VEGF inhibition and PD-1 blockade provides therapeutic opportunities for patients refractory to either therapy alone. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> We conducted a single-center, phase IB trial evaluating the safety and preliminary efficacy of toripalimab, a humanized immunoglobulin G<jats:sub>4<\/jats:sub> monoclonal antibody against PD-1 in combination with the VEGF receptor inhibitor axitinib in patients with advanced melanoma, including patients with chemotherapy-na\u00efve mucosal melanomas (88%). Patients received toripalimab at 1 or 3 mg\/kg via intravenous infusion every 2 weeks, in combination with axitinib 5 mg orally twice a day, in a dose-escalation and cohort-expansion study until confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. The primary objective was safety. Secondary objectives included efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and tumor tissue biomarkers. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Thirty-three patients were enrolled. No dose-limiting toxicities were observed. Ninety-seven percent of patients experienced treatment-related adverse events (TRAEs). The most common TRAEs were mild (grade 1 or 2) and included diarrhea, proteinuria, hand and foot syndrome, fatigue, AST or ALT elevation, hypertension, hypo- or hyperthyroidism, and rash. Grade 3 or greater TRAEs occurred in 39.4% of patients. By the cutoff date, among 29 patients with chemotherapy-na\u00efve mucosal melanoma, 14 patients (48.3%; 95% CI, 29.4% to 67.5%) achieved objective response, and the median progression-free survival time was 7.5 months (95% CI, 3.7 months to not reached) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> The combination of toripalimab plus axitinib was tolerable and showed promising antitumor activity in patients with treatment-na\u00efve metastatic mucosal melanoma. Patients enrolled in this study were all Asian, and this combination therapy must be validated in a randomized phase III trial that includes a non-Asian population before it can become a standard of care. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.19.00210","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T19:59:38Z","timestamp":1565639978000},"page":"2987-2999","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":160,"title":["Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G<sub>4<\/sub> Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial"],"prefix":"10.1200","volume":"37","author":[{"given":"Xinan","family":"Sheng","sequence":"first","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xieqiao","family":"Yan","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Chi","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Si","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanliang","family":"Cui","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bixia","family":"Tang","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siming","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Mao","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lian","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Kong","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Dai","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"OrigiMed, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongwen","family":"Tang","sequence":"additional","affiliation":[{"name":"Shanghai Junshi Biosciences, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaning","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Junshi Biosciences, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Junshi Biosciences, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Feng","sequence":"additional","affiliation":[{"name":"Shanghai Junshi Biosciences, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yao","sequence":"additional","affiliation":[{"name":"Shanghai Junshi Biosciences, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith T.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital and Institute, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19981015)83:8<1664::AID-CNCR23>3.0.CO;2-G"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/SAP.0000000000000731"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-85"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature22071"},{"key":"B5","first-page":"38","volume":"3","author":"Wang X","year":"2014","journal-title":"Linchuang Zhongliuxue Zazhi"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw694"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000306"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050092"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.2984"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2346"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.06.056"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4149\/neo_2017_419"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.746"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.9275"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.47.7836"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.161"},{"key":"B19","first-page":"2113","volume":"35","author":"Simonetti O","year":"2015","journal-title":"Anticancer Res"},{"key":"B20","first-page":"36","volume":"3","author":"Cui C","year":"2014","journal-title":"Linchuang Zhongliuxue Zazhi"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.7.4.449"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140559"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4493com"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12069"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0693-2"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-018-0725-9"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0312-8"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3593"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0053-3"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e3283457743"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.0170"},{"key":"B32","first-page":"35","volume":"3","author":"Kim KB","year":"2014","journal-title":"Chin Clin Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0575"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2012-0464"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.5694\/mja13.10448"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.09.007"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.9258"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nature25187"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91190"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30081-0"},{"key":"B42","volume":"36","author":"Lee C-H","year":"2018","journal-title":"J Clin Oncol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.66.1389"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.19.00210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T06:51:27Z","timestamp":1653807087000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.19.00210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,10]]},"references-count":40,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2019,11,10]]}},"alternative-id":["10.1200\/JCO.19.00210"],"URL":"https:\/\/doi.org\/10.1200\/jco.19.00210","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,10]]},"assertion":[{"value":"2019-07-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}