J Randolph Hecht, Jean-Marie Michot, David Bajor, Amita Patnaik, Ki Y Chung, Judy Wang, Gerald Falchook, James M Cleary, Richard Kim, Anuradha Krishnamurthy, Omkar Marathe, Hagop Youssoufian, Catherine Ellis, Angela Waszak, Srimoyee Ghosh, Hailei Zhang, Kaitlin Yablonski, Shruti D Shah, Ivan Diaz-Padilla, Susanna Ulahannan
{"title":"CITRINO:抗lag -3抗体encelimab单独或联合抗pd -1 dostarlimab治疗晚期/转移性实体瘤患者的1期剂量递增研究。","authors":"J Randolph Hecht, Jean-Marie Michot, David Bajor, Amita Patnaik, Ki Y Chung, Judy Wang, Gerald Falchook, James M Cleary, Richard Kim, Anuradha Krishnamurthy, Omkar Marathe, Hagop Youssoufian, Catherine Ellis, Angela Waszak, Srimoyee Ghosh, Hailei Zhang, Kaitlin Yablonski, Shruti D Shah, Ivan Diaz-Padilla, Susanna Ulahannan","doi":"10.1038/s44276-024-00118-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours.</p><p><strong>Methods: </strong>Part 1 (P1) involved dose escalation (20-720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers.</p><p><strong>Results: </strong>Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively.</p><p><strong>Conclusions: </strong>Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited.</p><p><strong>Clinical trial registration: </strong>NCT03250832.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"10"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868598/pdf/","citationCount":"0","resultStr":"{\"title\":\"CITRINO: phase 1 dose escalation study of anti-LAG-3 antibody encelimab alone or in combination with anti-PD-1 dostarlimab in patients with advanced/metastatic solid tumours.\",\"authors\":\"J Randolph Hecht, Jean-Marie Michot, David Bajor, Amita Patnaik, Ki Y Chung, Judy Wang, Gerald Falchook, James M Cleary, Richard Kim, Anuradha Krishnamurthy, Omkar Marathe, Hagop Youssoufian, Catherine Ellis, Angela Waszak, Srimoyee Ghosh, Hailei Zhang, Kaitlin Yablonski, Shruti D Shah, Ivan Diaz-Padilla, Susanna Ulahannan\",\"doi\":\"10.1038/s44276-024-00118-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours.</p><p><strong>Methods: </strong>Part 1 (P1) involved dose escalation (20-720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers.</p><p><strong>Results: </strong>Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively.</p><p><strong>Conclusions: </strong>Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited.</p><p><strong>Clinical trial registration: </strong>NCT03250832.</p>\",\"PeriodicalId\":519964,\"journal\":{\"name\":\"BJC reports\",\"volume\":\"3 1\",\"pages\":\"10\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868598/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BJC reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s44276-024-00118-x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BJC reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s44276-024-00118-x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
CITRINO: phase 1 dose escalation study of anti-LAG-3 antibody encelimab alone or in combination with anti-PD-1 dostarlimab in patients with advanced/metastatic solid tumours.
Background: Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours.
Methods: Part 1 (P1) involved dose escalation (20-720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers.
Results: Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively.
Conclusions: Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited.