{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:14:40Z","timestamp":1792793680954,"version":"4.5.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"25","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Patients with anti\u2013PD-1\u2013resistant melanoma (MEL) have no well-defined standard of care. BO-112 is a synthetic, double-stranded RNA (poly I:C) nanoplexed with polyethylenimine that when administered intratumorally has showed in patients with solid tumors potential to revert this resistance. We report efficacy and safety of the phase II clinical trial of intratumoral BO-112 plus intravenous pembrolizumab for patients with anti\u2013PD-1\u2013resistant MEL (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04570332\">NCT04570332<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Forty-two patients were treated with intratumoral BO-112 once every week for 7 weeks and then once every 3 weeks (up to 2 mg and up to eight lesions per treatment) combined with 200 mg pembrolizumab once every 3 weeks until progressive disease, unacceptable toxicity, death, or up to 1 year. Primary end point was RECIST 1.1 objective response rate (ORR) by independent central radiology review in modified intention-to-treat population (mITT; patients evaluable for response) with 20% ORR positivity threshold. Secondary key end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>For mITT, there were 40 patients and the ORR was 25%, with 10% complete, 15% partial, and 40% stable disease, with nonachieved (NA) median DOR (95% CI, 8.3 to NA). For ITT, there were 42 patients, and the median PFS and OS were 3.7 months (95% CI, 2.2 to 9.2) and NA (95% CI, 9.9 to NA), respectively, with 54% patients alive at 24 months. The combination was well tolerated: 16 patients (38.1%) experiencing \u2265G3-4 adverse events, four (9.5%) drug-related, and no deaths related to treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti\u2013PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti\u2013PD-1\u2013resistant scenario, with promising OS data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-24-02595","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T15:59:13Z","timestamp":1751039953000},"page":"2806-2815","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":17,"title":["BO-112 Plus Pembrolizumab for Patients With Anti\u2013PD-1\u2013Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04570332","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-668X","authenticated-orcid":true,"given":"Iv\u00e1n","family":"M\u00e1rquez-Rodas","sequence":"first","affiliation":[{"name":"Hospital General Universitario Gregorio Mara\u00f1on, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dutriaux","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6500-3507","authenticated-orcid":true,"given":"Philippe","family":"Saiag","sequence":"additional","affiliation":[{"name":"Department of General and Oncologic Dermatology, UVSQ, EA4340-BECCOH, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Ambroise-Par\u00e9 Hospital, Universit\u00e9 Paris-Saclay, Boulogne-Billancourt, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5333-0535","authenticated-orcid":true,"given":"Luis","family":"de la Cruz Merino","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy, Biomedicine Institute of Seville (IBIS)\/CSIC, Clinical Oncology Department, University Hospital Virgen Macarena and School of Medicine, University of Seville, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-4414","authenticated-orcid":true,"given":"Eduardo","family":"Casta\u00f1\u00f3n \u00c1lvarez","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-0238","authenticated-orcid":true,"given":"Caroline","family":"Robert","sequence":"additional","affiliation":[{"name":"Gustave Roussy and Universit\u00e9 Paris Saclay, Villejuif-Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7510-5059","authenticated-orcid":true,"given":"Juan F.","family":"Rodr\u00edguez-Moreno","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria HM Hospitales, Madrid, 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