{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:30:10Z","timestamp":1787056210677,"version":"build-2736575974"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100013119","name":"PharmaMar","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013119","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Lurbinectedin in combination with irinotecan showed synergistic antitumor activity in preclinical studies. A phase I\/II trial (NCT02611024) evaluated this combination in patients with advanced solid tumors. The phase II stage evaluated the antitumor activity of the recommended dose (RD) (lurbinectedin 2.0\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    on Day (D)1 plus irinotecan 75\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    on D1 and D8 q3wk with primary granulocyte colony-stimulating factor prophylaxis) in five tumor-specific cohorts. This pooled analysis describes the safety profile of this combination from 233 patients with different advanced solid tumors treated at the RD. Adverse events (AEs) and laboratory abnormalities were graded using NCI-CTCAE v.4. The most frequent AEs (any grade) related to treatment were fatigue (71% of patients\/25% of cycles), diarrhea (62%\/17%), nausea (59%\/18%), vomiting (35%\/7%) and decreased appetite (32%\/6%); the most common grade\u2009\u2265\u20093 AEs were fatigue (14%\/2%), diarrhea (14%\/2%) and febrile neutropenia (9%\/1%). The most common grade\u2009\u2265\u20093 laboratory abnormality regardless of relationship was neutropenia (53%). The rate of discontinuation due to treatment-related AEs was 3% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097 patients). There was one treatment-related death (0.4%) involving a 63-year-old male patient (0.4%) diagnosed with metastatic NEN who died due to grade 5 staphylococcal bacteremia. In conclusion, this pooled analysis shows a predictable and manageable safety profile for lurbinectedin in combination with irinotecan in patients with advanced solid tumors, with myelosuppression, fatigue and gastrointestinal disorders being the main toxicities observed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial code:<\/jats:bold>\n                    ClinicalTrials.gov identifier: NCT02611024.\n                  <\/jats:p>","DOI":"10.1007\/s10637-026-01616-0","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:39:59Z","timestamp":1777901999000},"page":"274-283","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pooled safety analysis of lurbinectedin plus irinotecan in patients with advanced solid tumors"],"prefix":"10.1007","volume":"44","author":[{"given":"Alejandro","family":"Falc\u00f3n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Cote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Molina-Cerrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Le Cesne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Bockorny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Paez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Martin-Broto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sant P.","family":"Chawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Kahatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Alfaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Siguero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Custodio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Alonso-Ordu\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Koll\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Soto-Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Paz-Ares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"1616_CR1","doi-asserted-by":"crossref","unstructured":"Galmarini C, Guillen MJ, Moneo V, Garc\u00e1 LF, Palomares M, Catalu\u00f1a O, Cuevas C, Aviles P (2013) Lurbinectedin (PM01183) synergizes with topoisomerase I inhibitors in vitro and in vivo. AACR American Association for Cancer Research; Annual Meeting; April 6\u201310, 2013. Washington, DC. Cancer Res 73(8 Supl 1) Abs N\u00ba 5499.","DOI":"10.1158\/1538-7445.AM2013-5499"},{"key":"1616_CR2","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1007\/s10637-025-01583-y","volume":"43","author":"A Falcon","year":"2025","unstructured":"Falcon A, Ponce S, Cote GM, Gil A, Lin JJ, Bockorny B, Martinez J, Kahatt C, Martinez S, Zubiaur P, Siguero M, Cullell-Young M, Jimenez J, Zugazagoitia J, Paz-Ares L (2025) Phase I results on the efficacy, safety and pharmacokinetics of lurbinectedin and irinotecan in advanced solid tumors. Invest New Drugs 43:955\u2013967","journal-title":"Invest New Drugs"},{"key":"1616_CR3","doi-asserted-by":"publisher","first-page":"8094","DOI":"10.1200\/JCO.2024.42.16_suppl.8094","volume":"42","author":"LG Paz-Ares","year":"2024","unstructured":"Paz-Ares LG, Gonzalez AF, Navarro A, Sanchez-Gastaldo A, Cote GM, Bockorny B, Molina-Cerrillo J, Artal A, Baena J, Gil A, Aix SP, Cabo HBd, Martinez S, Martinez JM, Lopez-Vilari\u00f1o JA, Kahatt CM, Zeaiter AH, Gomez J, Zugazagoitia J (2024) Efficacy and safety of lurbinectedin (LUR) with irinotecan (IRI) in patients (Pts) with relapsed small cell lung cancer (SCLC): Results from a phase 2 expansion cohort. J Clin Oncol 42:8094\u20138094","journal-title":"J Clin Oncol"},{"key":"1616_CR4","doi-asserted-by":"crossref","unstructured":"Ponce S, Ruiz-Torres M, Falcon A, Cote GM, Bernabe R, Lin JJ, Coya JM, Jimenez-Munoz M, Fernandez-Puyuelo P, Sanchez A, Zugazagoitia J, Ucero A, Baena J, Bote de Cabo H, Herrera M, Torres-Jimenez J, Zurera M, Kahatt C, Lopez-Vilarino JA, Martinez S, Siguero M, Malumbres M, Ferrer I, Paz-Ares L (2026) Combination of Lurbinectedin plus Irinotecan: Preclinical and Early Clinical Results in Relapsed Small Cell Lung Cancer Patients. J Thorac Oncol:103654.","DOI":"10.1016\/j.jtho.2026.103654"},{"key":"1616_CR5","doi-asserted-by":"publisher","first-page":"11560","DOI":"10.1200\/JCO.2024.42.16_suppl.11560","volume":"42","author":"GM Cote","year":"2024","unstructured":"Cote GM, Broto JM, Chawla SP, Bockorny B, Gonzalez AF, Pousa AL, Paz-Ares LG, Verret B, Martinez S, Extremera S, Cullell-Young M, Fudio S, Kahatt CM, Zeaiter AH, Cesne AL (2024) Efficacy and safety of lurbinectedin (LUR) with irinotecan (IRI) in a phase 2 expansion cohort of patients (Pts) with synovial sarcoma (SS). J Clin Oncol 42:11560\u201311560","journal-title":"J Clin Oncol"},{"key":"1616_CR6","doi-asserted-by":"crossref","unstructured":"Garcia-Carbonero R, Cote GM, Le Cesne A, Anton-Pascual B, Gordoa TA, Gonzalez AF, Torralvo AG, Martinez S, Siguero M, Cullell M, Fudio S, Zeaiter A, Cerrillo JM (2024) 27O Lurbinectedin plus irinotecan in pre-treated gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs). ESMO Open 9.","DOI":"10.1016\/j.esmoop.2024.102416"},{"key":"1616_CR7","doi-asserted-by":"crossref","unstructured":"Besse B, Paz-Ares LG, Peters S, Cappuzzo F, Reck M, Calles A, Califano R, Lopez-Vilari\u00f1o JA, Veramendi S, Kahatt CM, Zeaiter AH, Sands J (2023) A phase III study of lurbinectedin alone or in combination with irinotecan vs investigator's choice (topotecan or irinotecan) in patients with relapsed small cell lung cancer (SCLC; LAGOON trial). Journal of Clinical Oncology 41:TPS8613-TPS8613.","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS8613"},{"key":"1616_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.113259","volume":"192","author":"A Leary","year":"2023","unstructured":"Leary A, Oaknin A, Trigo JM, Moreno V, Delord JP, Boni V, Brana I, Fernandez C, Kahatt C, Nieto A, Cullell-Young M, Zeaiter A, Subbiah V (2023) Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. Eur J Cancer 192:113259","journal-title":"Eur J Cancer"},{"key":"1616_CR9","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1080\/14796694.2025.2463798","volume":"21","author":"GM Cote","year":"2025","unstructured":"Cote GM, Chawla SP, Demetri G, Kasper B, Jones RL, Broto JM, Wooley J, Weiss MC, Tafuto S, Badalamenti G, Carrasco I, Peinado P, Blay JY, Boggio G, Fernandez C, Nieto A, Kahatt C, Alfaro V, Le Cesne A (2025) SaLudo: a randomized phase IIb\/III study of lurbinectedin plus doxorubicin as first-line treatment in leiomyosarcoma. Future Oncol 21:943\u2013951","journal-title":"Future Oncol"},{"key":"1616_CR10","first-page":"48","volume":"12","author":"HC Pitot","year":"1998","unstructured":"Pitot HC (1998) US pivotal studies of irinotecan in colorectal carcinoma. 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No individual patient data are included in this article that could be used to identify any individual.","order":3,"name":"Ethics","label":"Consent to publish","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"A. Falc\u00f3n reports advisory role for Roche, Pfizer, Menarini, AstraZeneca, and MSD; honoraria from Roche, Pfizer, Novartis, Lilly, Menarini, AstraZeneca, MSD, Daiichi, Gilead, Dr. Reddy, and Grunenthal; and travel accommodations from Novartis, Daiichi, Gilead, and Roche. G.M. Cote reports honoraria from Gilead, the Chordoma Foundation, and the Pharma Mar Foundation; Ad hoc Scientific Advisory Board for Ikena Oncology, C4 Therapeutics, Daiichi Sankyo Inc, Pharma Mar and Parabilis; Institutional research funding to MGH for the conduct of clinical trials from Pharma Mar, MacroGenics, Eisai, Merck KGaA\/EMD Serono Research and Development Institute, Repare Therapeutics, Foghorn Therapeutics, Jazz Pharmaceuticals, BioAtla, Inhibrx, Ikena Oncology, C4 Therapeutics, and Pyxis; and travel accommodations from Pharma Mar. J. Molina-Cerrillo reports consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen, BMS, Exelisis, MSD, Adium, Astellas, Recordati Rare Diseases, Eisai and Novartis; and research grants from Pfizer, IPSEN, Janssen and Roche outside the submitted work. A. LeCesne reports bureau fees for Deciphera. P. Rocha reports personal fees for invited speaker roles from Amgen, AstraZeneca, Daiichi Sankyo, and ThermoFisher; advisory boards for Daiichi Sankyo and IGES Pharma; and ceived congress registration and travel support from AstraZeneca, BMS, Kyowa Kirin, Lilly, MSD, PharmaMar, and Roche. B. Bockorny reports Research Funding from Agenus Inc and NanoView Bioscience; travel expenses from Erytech Pharma and Agenus; Advisory Board and Consulting from SpringWorks, Blueprint Medicines, BioLine Rx, Boxer, Enlivex, Rango and N1X10; and Speaker bureau from Total Health. D. P\u00e1ez reports consultant, advisory or speaker roles for Amgen, AAA, Terumo, Takeda and MSD and research funding from Merck outside the submitted work. J. Martin-Broto reports personal funding from Pharma Mar (expert testimony, advisory, and invited speaker), Tecnofarma (advisory), Deciphera (advisory), Amgem (expert testimony), Asofarma (advisory), Bayer (expert testimony), Boehringer Ingelheim (expert testimony), Cogent (advisory), GSK (expert testimony), Roche (expert testimony), Sarcoma Research Solutions SL (profits); institutional funding for research support (clinical trials or translational) from Pharma Mar, Eli Lilly and Company, Adaptimmune Therapeutics, Lixte, Karyopharm, Deciphera, GSK, AYALA, INBRX, PTC Therapeutics, RAIN Therapeutics, Boehringher, Phyllogen, Abiskko, BMS, Pfizer, COGENT Therapeutics, Synox Therapeutics, Servier, Karyopharm, Lixte, Biosplice, Cebiotex, IMMIX, and Springworks Therapeutics; and non-remunerated leadership roles for SELNET, and non-remunerated membership or affiliation with ESMO, SEOM, GEIS, ASCO, CTOS and EORTC. S.P. Chawla is employee at the Sant P. Chawla, MD, Inc, and reports stock ownership for AADi, Cellestia Biotech, CounterPoint, and Immix Biopharma; honoraria for AADi and SpringWorks; consulting or advisory role for AADi, Cellestia Biotech, and SpringWorks; speaker\u2019s bureau for AADi and SpringWorks; research funding, patents, royalties and other intellectual property and travel and accommodation expenses from Amgen, Roche, Threshold Pharmaceuticals, CytRx Corporation, Ignyla, Immune Design, TRACIN Pharma, and Karyoph. S. Martinez, and M. Siguero are employees of Pharma Mar. C. Kahatt, J. Jimenez and V. Alfaro are employees and stock owners of Pharma Mar. C. L\u00f3pez reports consultant or advisor role for Roche, AstraZeneca, MSD, BMS, Ipsen, Lilly, and Eisai; research funding from Roche, AstraZeneca, MSD, BMS, and Ipsen; and speaking honoraria from A. Koll\u00e1r reports advisory role for Pharma Mar, Merck and travel grants for Pharma mmar, Deciphera, Amgen, Roche, AstraZeneca, MSD, BMS, Eisai, Lilly, and Ipsen. L. Paz-Ares reports co-founder position and member of board of directors with Altum Sequencing, and Stab therapeutics; consulting fees or advisory role for Abbvie, Amgen, AstraZeneca, Bayer, Beigene, Biontech, Bristol-Myers-Squibb, Boehringer-Ingelheim, Daiichi-Sankyo, Glaxo-SmithKline, Gilead, Johnson & Johnson, Lilly, MSD, Merck-Serono, Mirati, Novartis, Pharma Mar, Pfizer, Regeneron, Roche, Sanofi, and Takeda; speakers\u2019bureau for MSD Oncology, BMS, Roche\/Genentech, Pfizer, Lilly, AstraZeneca, and Merck Serono; and institutional research funding from BMS, AstraZeneca, Pharma Mar, MSD, and Pfizer during the conduct of the study. Other authors declared no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}