{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:57:21Z","timestamp":1793372241758,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer cachexia is a multifactorial metabolic wasting syndrome characterized by anorexia, unintentional loss of weight involving both skeletal muscle and adipose tissues, progressive functional impairment and reduced survival. Therapeutic strategies for this serious condition are very limited. Growth differentiation factor 15 (GDF\u201015) is a cytokine that is implicated in cancer cachexia and may represent both a biomarker of cancer cachexia and a potential therapeutic target. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF\u201015\u2010mediated signalling. Preclinical and preliminary phase 1 data suggest that ponsegromab\u2010mediated inactivation of circulating GDF\u201015 may lead to improvement in key characteristics of cachexia. The primary objective of this phase 2 study is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia and elevated GDF\u201015 concentrations. Secondary objectives include assessing physical activity, physical function, actigraphy, appetite, nausea and vomiting, fatigue and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, immunogenicity, lumbar skeletal muscle index and Response Evaluation Criteria in Solid Tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Approximately 168 adults with non\u2010small\u2010cell lung, pancreatic or colorectal cancers who have cachexia and elevated GDF\u201015 concentrations will be randomized in a double\u2010blind, placebo\u2010controlled study (NCT05546476). Participants meeting eligibility criteria will be randomized 1:1:1:1 to one of three dose groups of ponsegromab (100, 200 or 400\u00a0mg) or matching placebo administered subcutaneously every 4\u00a0weeks for an initial 12\u2010week treatment period. This is followed by optional open\u2010label treatment with ponsegromab of 400\u00a0mg administered every 4\u00a0weeks for up to 1\u00a0year. The primary endpoint is mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian E<jats:sub>max<\/jats:sub> model will be used for the primary analysis. Secondary endpoints include physical activity, physical function and actigraphy measured by remote digital sensors; patient\u2010reported appetite\u2010related symptoms assessed by Functional Assessment of Anorexia\u2010Cachexia Therapy subscale scores; anorexia\/appetite, nausea and vomiting, and fatigue evaluated according to questions from the Cancer\u2010Related Cachexia Symptom Diary; and incidence of adverse events, safety laboratory tests, vital signs and electrocardiogram abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Perspective<\/jats:title><jats:p>Cancer\u2010related cachexia is an area of significant unmet medical need. This study will support the clinical development of ponsegromab as a novel inhibitor of GDF\u201015, which may ameliorate key pathologies of cancer cachexia to improve patient symptoms, functionality and quality of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> ID: NCT05546476.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13435","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T05:42:37Z","timestamp":1710826957000},"page":"1054-1061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC\u20101 study design"],"prefix":"10.1002","volume":"15","author":[{"given":"John D.","family":"Groarke","sequence":"first","affiliation":[{"name":"Internal Medicine Research Unit Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Crawford","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susie M.","family":"Collins","sequence":"additional","affiliation":[{"name":"Global Biometrics and Data Management Pfizer R&amp;D UK Ltd  Sandwich Kent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon L.","family":"Lubaczewski","sequence":"additional","affiliation":[{"name":"Early Clinical Development and Biomedicine Artificial Intelligence Pfizer Inc  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danna M.","family":"Breen","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Global Access and Value Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Global Product Development Pfizer Inc  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Revkin","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle I.","family":"Rossulek","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi R.","family":"Saxena","sequence":"additional","affiliation":[{"name":"Internal Medicine Research Unit Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100092"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00611"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02232-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12402"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022020-045449"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115372"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.023"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.07.018"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4393"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4392"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4394"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06249-4"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.11.008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21309-x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12033"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12077"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111947"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13219"},{"key":"e_1_2_7_21_1","unstructured":"ClinicalTrials.gov.NCT03599063: single dose first in human study of PF\u201006946860 in healthy adult subjects.2018. 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