{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:31:15Z","timestamp":1791779475621,"version":"4.3.4"},"reference-count":32,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"CytomX Therapeutics, Inc."}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2021,5,2]]},"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Probody\u00ae therapeutics are antibody prodrugs designed to be activated by tumor-associated proteases. This conditional activation restricts antibody binding to the tumor microenvironment, thereby minimizing \u2018off-tumor\u2019 toxicity. Here, we report the phase 1 data from the first-in-human study of CX-072 (pacmilimab), a Probody immune checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1), in combination with the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adults (n=27) with advanced solid tumors (naive to PD-L1\/programmed cell death protein 1 or CTLA-4 inhibitors) were enrolled in the phase 1 combination therapy dose-escalation portion of this multicenter, open-label, phase 1\/2 study (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03013491\">NCT03013491<\/jats:ext-link>). Dose-escalation pacmilimab\/ipilimumab followed a standard 3+3 design and continued until the maximum tolerated dose (MTD) was determined. Pacmilimab+ipilimumab was administered intravenously every 3 weeks for four cycles, followed by pacmilimab administered every 2 weeks as monotherapy. The primary objective was identification of dose-limiting toxicities and determination of the MTD. Other endpoints included the rate of objective response (Response Evaluation Criteria In Solid Tumors v.1.1).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty-seven patients were enrolled in pacmilimab (mg\/kg)+ipilimumab (mg\/kg) dose-escalation cohorts: 0.3+3 (n=6); 1+3 (n=3); 3+3 (n=3); 10+3 (n=8); 10+6 (n=6); and 10+10 (n=1). Dose-limiting toxicities occurred in three patients, one at the 0.3+3\u2009dose level (grade 3 dyspnea\/pneumonitis) and two at the 10+6\u2009dose level (grade 3 colitis, grade 3 increased aspartate aminotransferase). The MTD and recommended phase 2 dose was pacmilimab 10\u2009mg\/kg+ipilimumab 3\u2009mg\/kg administered every 3 weeks. Pacmilimab-related grade 3\u20134 adverse events (AEs) and grade 3\u20134 immune-related AEs were reported in nine (33%) and six (22%) patients, respectively. Three patients (11%) discontinued treatment because of AEs. The overall response rate was 19% (95% CI 6.3 to 38.1), with one complete (anal squamous cell carcinoma) and four partial responses (cancer of unknown primary, leiomyosarcoma, mesothelioma, testicular cancer). Responses lasted for &gt;12 months in four patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The MTD and recommended phase 2 dose of pacmilimab (10\u2009mg\/kg)+ipilimumab (3\u2009mg\/kg) every 3 weeks is active and has a favorable tolerability profile.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2021-002446","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T13:33:53Z","timestamp":1627047233000},"page":"e002446","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["CX-072 (pacmilimab), a Probody PD-L1 inhibitor, in combination with ipilimumab in patients with advanced solid tumors (PROCLAIM-CX-072): a first-in-human, dose-finding study"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct03013491","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03013491","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0542-6054","authenticated-orcid":false,"given":"Rachel E","family":"Sanborn","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth GE","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Universitair Medisch Centrum Groningen, University of Groningen, Groningen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A","family":"Ott","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Garcia-Corbacho","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Clinic Barcelona\/IDIBAPS, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Boni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, START Madrid-CIOCC, Hospital Universitario HM Sanchinarro, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Bendell","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute\/Tennessee Oncology, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A","family":"Autio","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Plummer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Northern Centre for Cancer Care, Newcastle Hospitals NHS Trust and Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stroh","sequence":"additional","affiliation":[{"name":"CytomX Therapeutics Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Lu","sequence":"additional","affiliation":[{"name":"CytomX Therapeutics Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Thistlethwaite","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Christie Hospital NHS Foundation Trust and University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"2025100311554202000_9.7.e002446.1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13045-019-0779-5","article-title":"Immune checkpoint inhibitors of PD-L1 as cancer therapeutics","volume":"12","author":"Akinleye","year":"2019","journal-title":"J Hematol Oncol"},{"key":"2025100311554202000_9.7.e002446.2","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12030738","article-title":"Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence","volume":"12","author":"Vaddepally","year":"2020","journal-title":"Cancers"},{"key":"2025100311554202000_9.7.e002446.3","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.20833","article-title":"Assessment of clinical activity of PD-1 checkpoint inhibitor combination therapies reported in clinical 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CX-072 (pacmilimab), a probody PD-L1 inhibitor, in advanced or recurrent solid tumors (PROCLAIM-CX-072): an open label dose-finding and first-inhuman study. J Immunother Cancer 2021.doi:10.1136\/jitc-2021-002447","DOI":"10.1136\/jitc-2021-002447"},{"key":"2025100311554202000_9.7.e002446.26","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30428-X"},{"key":"2025100311554202000_9.7.e002446.27","unstructured":"Bristol Myers Squibb . 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