{"doi":"10.1177/17588359251339930","title":"NEXUS: a phase I dose escalation study of selinexor plus nivolumab and ipilimumab in Asian patients with advanced/metastatic solid malignancies","abstract":"<jats:sec>\n                    <jats:title>Background:</jats:title>\n                    <jats:p>Selinexor (SEL) is an oral inhibitor of nuclear export protein Exportin 1 (XPO1) previously shown to upregulate programmed cell death protein 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:</jats:title>\n                    <jats:p>To investigate the safety and antitumor activity of SEL, nivolumab (NIVO), and ipilimumab (IPI) in Asian patients with treatment-refractory solid organ cancers.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:</jats:title>\n                    <jats:p>Phase I study of escalating doses of SEL in combination with NIVO + IPI. Patients were enrolled in a 3 + 3 design.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:</jats:title>\n                    <jats:p>NIVO and IPI were dosed at 240 mg Q2W and 1 mg/kg Q6W, respectively. SEL was dosed with a 2-week monotherapy run-in prior to triplet therapy, at dose levels (DL) 1 (40 mg once/week) and DL2 (60 mg once/week). Dose-limiting toxicity (DLT) was assessed over the first 6 weeks.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:</jats:title>\n                    <jats:p>\n                      Twelve patients were enrolled; 11 were evaluable for response, and 6 were evaluable for DLT (1 had a non-treatment-related stroke and 5 had progressive disease (PD) prior to completion of the DLT period). The median age was 64.5 (range 39–78) years. The median line of prior therapy was 3 (range 2–5). Dose escalation proceeded through DL1 (\n                      <jats:italic toggle=\"yes\">n</jats:italic>\n                       = 7, 3 evaluable for DLT) and DL2 (\n                      <jats:italic toggle=\"yes\">n</jats:italic>\n                       = 5, 3 evaluable for DLT). No DLTs were observed among evaluable patients. No patients required dose reduction of SEL. Most frequent treatment-related AEs were fatigue (5/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 1), nausea (5/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0), anorexia (4/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0), transaminitis (2/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0), and hypomagnesemia (2/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0). The recommended phase II dose was SEL 60 mg once/week combined with NIVO + IPI. One patient had a partial response (PR; progression-free survival (PFS) of 61 days), 3 had prolonged stable disease (SD; PFS of 141, 344, and 442 days, respectively), and 7 had PD. All patients with SD or PR had previously progressed on immunotherapy but experienced prolonged disease control on SEL in combination with NIVO + IPI.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:</jats:title>\n                    <jats:p>SEL in combination with NIVO + IPI was well tolerated without any new safety signals. The combination showed promising and durable antitumor activity in Asian patients with advanced malignancies who had failed prior immunotherapy and merits further investigation.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:</jats:title>\n                    <jats:p>\n                      NCT04850755 (\n                      <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT04850755\">https://clinicaltrials.gov/study/NCT04850755</jats:ext-link>\n                      ).\n                    </jats:p>\n                  </jats:sec>","journal":"Therapeutic Advances in Medical Oncology","year":2025,"id":652101,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1700943,"name":"Santhiay Nathan Jeraj","orcid":null,"position":1,"is_corresponding":false},{"id":1027729,"name":"Raghav Sundar","orcid":"0000-0001-9423-1368","position":2,"is_corresponding":false},{"id":669376,"name":"Wei Peng Yong","orcid":"0000-0003-4404-3777","position":3,"is_corresponding":false},{"id":1700944,"name":"Matilda Lee","orcid":null,"position":4,"is_corresponding":false},{"id":432950,"name":"Yiqing Huang","orcid":null,"position":5,"is_corresponding":false},{"id":1700945,"name":"Yugarajah Asokumaran","orcid":null,"position":6,"is_corresponding":false},{"id":1700946,"name":"Gloria H. J. Chan","orcid":null,"position":7,"is_corresponding":false},{"id":1700947,"name":"Natalie Y. L. Ngoi","orcid":null,"position":8,"is_corresponding":false},{"id":1700948,"name":"Andrea L. A. Wong","orcid":null,"position":9,"is_corresponding":false},{"id":321564,"name":"Ross A. Soo","orcid":"0000-0002-3053-3997","position":10,"is_corresponding":false},{"id":639046,"name":"Cheng Ean Chee","orcid":"0000-0003-2385-7712","position":11,"is_corresponding":false},{"id":1700949,"name":"Joline S. J. Lim","orcid":null,"position":12,"is_corresponding":false},{"id":816875,"name":"Boon Cher Goh","orcid":"0000-0002-4107-102X","position":13,"is_corresponding":false},{"id":344382,"name":"Soo Chin Lee","orcid":"0000-0002-5835-6419","position":14,"is_corresponding":false},{"id":638635,"name":"David S.P. Tan","orcid":"0000-0001-9087-5262","position":15,"is_corresponding":false},{"id":1700942,"name":"Joan R. Choo","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"NEXUS: a phase I dose escalation study of selinexor plus nivolumab and ipilimumab in Asian patients with advanced/metastatic solid malignancies","abstract":"<jats:sec>\n                    <jats:title>Background:</jats:title>\n                    <jats:p>Selinexor (SEL) is an oral inhibitor of nuclear export protein Exportin 1 (XPO1) previously shown to upregulate programmed cell death protein 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:</jats:title>\n                    <jats:p>To investigate the safety and antitumor activity of SEL, nivolumab (NIVO), and ipilimumab (IPI) in Asian patients with treatment-refractory solid organ cancers.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:</jats:title>\n                    <jats:p>Phase I study of escalating doses of SEL in combination with NIVO + IPI. Patients were enrolled in a 3 + 3 design.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:</jats:title>\n                    <jats:p>NIVO and IPI were dosed at 240 mg Q2W and 1 mg/kg Q6W, respectively. SEL was dosed with a 2-week monotherapy run-in prior to triplet therapy, at dose levels (DL) 1 (40 mg once/week) and DL2 (60 mg once/week). Dose-limiting toxicity (DLT) was assessed over the first 6 weeks.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:</jats:title>\n                    <jats:p>\n                      Twelve patients were enrolled; 11 were evaluable for response, and 6 were evaluable for DLT (1 had a non-treatment-related stroke and 5 had progressive disease (PD) prior to completion of the DLT period). The median age was 64.5 (range 39–78) years. The median line of prior therapy was 3 (range 2–5). Dose escalation proceeded through DL1 (\n                      <jats:italic toggle=\"yes\">n</jats:italic>\n                       = 7, 3 evaluable for DLT) and DL2 (\n                      <jats:italic toggle=\"yes\">n</jats:italic>\n                       = 5, 3 evaluable for DLT). No DLTs were observed among evaluable patients. No patients required dose reduction of SEL. Most frequent treatment-related AEs were fatigue (5/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 1), nausea (5/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0), anorexia (4/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0), transaminitis (2/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0), and hypomagnesemia (2/12;\n                      <jats:italic toggle=\"yes\">G</jats:italic>\n                       ⩾ 3 = 0). The recommended phase II dose was SEL 60 mg once/week combined with NIVO + IPI. One patient had a partial response (PR; progression-free survival (PFS) of 61 days), 3 had prolonged stable disease (SD; PFS of 141, 344, and 442 days, respectively), and 7 had PD. All patients with SD or PR had previously progressed on immunotherapy but experienced prolonged disease control on SEL in combination with NIVO + IPI.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:</jats:title>\n                    <jats:p>SEL in combination with NIVO + IPI was well tolerated without any new safety signals. The combination showed promising and durable antitumor activity in Asian patients with advanced malignancies who had failed prior immunotherapy and merits further investigation.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:</jats:title>\n                    <jats:p>\n                      NCT04850755 (\n                      <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT04850755\">https://clinicaltrials.gov/study/NCT04850755</jats:ext-link>\n                      ).\n                    </jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40502306","pmcid":"PMC12152386","openalex_id":"https://openalex.org/W4411144672","authors":[],"funders":[{"funder_name":"Singapore Ministry of Health’s National Medical Research Council under its National Medical Research Council (NMRC) Clinician Scientist Award Senior Investigator Grant","grant_id":"CSASI21jun-0003","title":null},{"funder_name":"Karyopharm Therapeutics","grant_id":"","title":null}],"total_grants":2,"fwci":0.4238,"citation_percentile":0.59086331,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.1177/17588359251339930","host_type":"journal"},{"url":"https://doi.org/10.1177/17588359251339930","host_type":"publisher"},{"url":"https://journals.sagepub.com/doi/pdf/10.1177/17588359251339930","host_type":"publisher"},{"url":"https://journals.sagepub.com/doi/full-xml/10.1177/17588359251339930","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40502306","host_type":"repository"},{"url":"https://doaj.org/article/2f7ca5184c88417e883f5101f7f07705","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12152386","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12152386","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12152386?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Nuclear Structure and Function","Retinoids in leukemia and cellular processes","Cell death mechanisms and regulation"],"mesh_terms":[],"keywords":["Medicine","Ipilimumab","Nivolumab","Nausea","Internal medicine","Toxicity","Progressive disease","Renal cell carcinoma","Refractory (planetary science)","Response Evaluation Criteria in Solid Tumors","Oncology","Gastroenterology","Phases of clinical research","Cancer","Immunotherapy","Chemotherapy","Clinical Trials","Combination Immunotherapy","Phase I Trials","Selinexor","Immunotherapy Resistance"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T11:56:14.095798Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}