{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:24:05Z","timestamp":1790900645834,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Bone metastases are common complications of solid tumors. The outcome is poor despite major progress in cancer therapies. We describe a multicenter, open-label, phase 1, dose escalation and expansion trial of JMT103, a novel fully humanized receptor activator of nuclear factor kappa-B ligand (RANKL)-targeting monoclonal antibody, in adults with bone metastases from solid tumors. The study assessed the safety, tolerability, and pharmacokinetics\/pharmacodynamics of JMT103. Patients received JMT103 at doses of 0.5, 1.0, 2.0, and 3.0 mg\/kg every 4 weeks for 3 cycles. Among 59 patients enrolled, 20 and 39 patients participated in the dose-escalation and dose-expansion phases, respectively. One dose-limiting toxicity was observed at 2.0 mg\/kg. The maximum tolerated dose was not determined. Treatment-related adverse events were reported in 29 (49.2%) patients, most commonly hypophosphatemia (30.5%), hypocalcemia (23.7%), and hypermagnesemia (10.2%). No treatment-related serious adverse events were reported. Two patients died due to disease progression, which were attributed to gastric cancer and lung neoplasm malignant respectively. Dose proportionality occurred between exposure levels and administered dose was within a dose range of 0.5 to 3.0 mg\/kg. The suppression of urinary N-telopeptide corrected for creatinine was rapid, significant, and sustained across all doses of JMT103, with the median change from baseline ranging from \u201361.4% to \u201392.2% at day 141. JMT103 was well tolerated in patients with bone metastases from solid tumors, with a manageable safety profile. Bone antiresorptive activity shows the potential of JMT103 for treatment of bone metastases from solid tumors.<\/jats:p><jats:p>Registration No.: NCT03550508; URL: <jats:uri>https:\/\/www.clinicaltrials.gov\/<\/jats:uri><\/jats:p>","DOI":"10.3389\/fonc.2022.971594","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T19:11:05Z","timestamp":1659726665000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Safety, tolerability, and pharmacokinetics\/pharmacodynamics of JMT103 in patients with bone metastases from solid tumors"],"prefix":"10.3389","volume":"12","author":[{"given":"Xu","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junli","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiong","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiugao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhufeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/ctrv.2000.0210","article-title":"Metastatic bone disease: Clinical features, pathophysiology and treatment strategies","volume":"27","author":"Coleman","year":"2001","journal-title":"Cancer Treat Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc867","article-title":"Metastasis to bone: Causes, consequences and therapeutic opportunities","volume":"2","author":"Mundy","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3055","article-title":"Cancer to bone: A fatal attraction","volume":"11","author":"Weilbaecher","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1152\/physrev.00012.2019","article-title":"Bone metastasis: Mechanisms, therapies, and biomarkers","volume":"101","author":"Cl\u00e9zardin","year":"2021","journal-title":"Physiol Rev Am Physiol Soc"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0931","article-title":"Clinical features of metastatic bone disease and risk of skeletal morbidity","volume":"12","author":"Coleman","year":"2006","journal-title":"Clin Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10195-015-0344-0","article-title":"Bone metastases of unknown origin: Epidemiology and principles of management","volume":"16","author":"Piccioli","year":"2015","journal-title":"J Orthop Traumatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2017.7024","article-title":"Frequency, morbidity, and mortality of bone metastases in advanced hepatocellular carcinoma","volume":"16","author":"Harding","year":"2018","journal-title":"J Natl Compr Canc Netw"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra030831","article-title":"Mechanisms of bone metastasis","volume":"350","author":"Roodman","year":"2004","journal-title":"New Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp042806","article-title":"Clinical practice. hypercalcemia associated with cancer","volume":"352","author":"Stewart","year":"2005","journal-title":"New Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4081\/oncol.2017.321","article-title":"Bone metastases: An overview","volume":"11","author":"Macedo","year":"2017","journal-title":"Oncol Rev"},{"key":"B11","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ebiom.2019.06.047","article-title":"Combinatorial targeting of cancer bone metastasis using mrna engineered stem cells","volume":"45","author":"Segaliny","year":"2019","journal-title":"EBioMedicine"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol28050290","article-title":"Current overview of treatment for metastatic bone disease","volume":"28","author":"Tsukamoto","year":"2021","journal-title":"Curr Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.diii.2020.12.008","article-title":"Percutaneous thermal ablation of sacral metastases: Assessment of pain relief and local tumor control","volume":"102","author":"Cazzato","year":"2021","journal-title":"Diagn Interv Imaging"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-022-06990-y","article-title":"3-T magnetic resonance-guided high-intensity focused ultrasound (3 t-Mr-Hifu) for the treatment of pain from bone metastases of solid tumors","volume":"30","author":"Bongiovanni","year":"2022","journal-title":"Supportive Care Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu103","article-title":"Bone health in cancer patients: Esmo clinical practice guidelines","author":"Coleman","year":"2014","journal-title":"Ann Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.75.4614","article-title":"Role of bone-modifying agents in metastatic breast cancer: An American society of clinical oncology-cancer care Ontario focused guideline update","volume":"35","author":"Van Poznak","year":"2017","journal-title":"J Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13046-017-0578-1","article-title":"Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials","volume":"36","author":"Gdowski","year":"2017","journal-title":"J Exp Clin Cancer Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.11.020","article-title":"Denosumab and bisphosphonates: Different mechanisms of action and effects","volume":"48","author":"Baron","year":"2011","journal-title":"Bone"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S14566","article-title":"Denosumab, a rank ligand inhibitor, for the management of bone loss in cancer patients","volume":"7","author":"Yee","year":"2012","journal-title":"Clin Interv Aging"},{"key":"B20","unstructured":"LiuJ\n          2015"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.7101","article-title":"Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: A randomized, double-blind study","volume":"28","author":"Stopeck","year":"2010","journal-title":"J Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(10)62344-6","article-title":"Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A randomised, double-blind study","volume":"377","author":"Fizazi","year":"2011","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.31.3304","article-title":"Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (Excluding breast and prostate cancer) or multiple myeloma","volume":"29","author":"Henry","year":"2011","journal-title":"J Clin Oncol"},{"key":"B24","unstructured":"FOOD & DRUG ADMINISTRATION Amgen IncFull prescribing information for xgeva (Denosumab) injection U.S2020"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1933","article-title":"A study of the biological receptor activator of nuclear factor-kappab ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer","volume":"12","author":"Body","year":"2006","journal-title":"Clin Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.8604","article-title":"Randomized active-controlled phase ii study of denosumab efficacy and safety in patients with breast cancer-related bone metastases","volume":"25","author":"Lipton","year":"2007","journal-title":"J Clin Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.08.007","article-title":"A randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab administered subcutaneously to postmenopausal Japanese women","volume":"49","author":"Kumagai","year":"2011","journal-title":"Bone"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197984","article-title":"Pharmacokinetics, pharmacodynamics, safety, and tolerability of single-dose denosumab in healthy Chinese volunteers: A randomized, single-blind, placebo-controlled study","volume":"13","author":"Chen","year":"2018","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2008.00803.x","article-title":"Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer-related bone metastases","volume":"99","author":"Yonemori","year":"2008","journal-title":"Cancer Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2002.20.3.850","article-title":"Prospective evaluation of the peptide-bound collagen type I cross-links n-telopeptide and c-telopeptide in predicting bone metastases status","volume":"20","author":"Costa","year":"2002","journal-title":"J Clin Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601437","article-title":"Bone resorption predicts for skeletal complications in metastatic bone disease","volume":"89","author":"Brown","year":"2003","journal-title":"Br J Cancer"},{"key":"B32","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1093\/jnci\/dji002","article-title":"Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors","volume":"97","author":"Brown","year":"2005","journal-title":"J Natl Cancer Inst"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.2146","article-title":"Randomized phase ii trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates","volume":"27","author":"Fizazi","year":"2009","journal-title":"J Clin Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-014-1247-x","article-title":"Differences of osteoblastic bone metastases and osteolytic bone metastases in clinical features and molecular characteristics","volume":"17","author":"Fang","year":"2015","journal-title":"Clin Transl Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12355","article-title":"The pharmacokinetics and pharmacodynamics of denosumab in patients with advanced solid tumours and bone metastases: A systematic review","volume":"78","author":"Sohn","year":"2014","journal-title":"Br J Clin Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1586\/14737167.2015.1024662","article-title":"Racial variation in the clinical and economic burden of skeletal-related events among elderly men with stage iv metastatic prostate cancer","volume":"15","author":"Jayasekera","year":"2015","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/jso.26765","article-title":"Sex, Racial\/Ethnic and socioeconomic disparities in patients with metastatic bone disease","volume":"125","author":"Jawad","year":"2022","journal-title":"J Surg Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/13557858.2020.1734775","article-title":"Racial disparities in bone metastasis patterns and targeted screening and treatment strategies in newly diagnosed lung cancer patients","volume":"27","author":"Xu","year":"2022","journal-title":"Ethn Health"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.11526","article-title":"Efficacy and safety of Jmt103 in patients with giant cell tumor of bone: A multicenter, single-arm, open-label, phase Ib\/Ii study","volume":"39","author":"Niu","year":"2021","journal-title":"J Clin Oncol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/s0024-3205(03)00434-x","article-title":"Expression of vegf and mmp-9 in giant cell tumor of bone and other osteolytic lesions","volume":"73","author":"Kumta","year":"2003","journal-title":"Life Sci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17111827","article-title":"The effect of everolimus in an in vitro model of triple negative breast cancer and osteoclasts","volume":"17","author":"Mercatali","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(21)00387-9","article-title":"Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (Itcc-050): A multicentre, open-label, multicohort, phase 1\/2 study","volume":"22","author":"Gaspar","year":"2021","journal-title":"Lancet Oncol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"372","DOI":"10.3390\/biomedicines10020372","article-title":"A rationale for the activity of bone target therapy and tyrosine kinase inhibitor combination in giant cell tumor of bone and desmoplastic fibroma: Translational evidences","volume":"10","author":"De Vita","year":"2022","journal-title":"Biomedicines"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ijc.33613","article-title":"Final results of the randomized phase 2 Leo trial and bone protective effects of everolimus for premenopausal hormone receptor-positive, Her2-negative metastatic breast cancer","author":"Jeong","year":"2021","journal-title":"Int J Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.971594\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T19:11:08Z","timestamp":1659726668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.971594\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,5]]},"references-count":44,"alternative-id":["10.3389\/fonc.2022.971594"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.971594","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,5]]},"article-number":"971594"}}