Jyoti Malhotra MD, MPH , Yong Lin PhD , Malini Patel MD , Michael J. Yellin MD , Emmanuel Zachariah PhD , Curtis Krier PhD , Ankit Saxena PhD , Salma K. Jabbour MD
{"title":"Atezolizumab和Varlilumab联合放疗治疗转移性NSCLC患者的I期试验","authors":"Jyoti Malhotra MD, MPH , Yong Lin PhD , Malini Patel MD , Michael J. Yellin MD , Emmanuel Zachariah PhD , Curtis Krier PhD , Ankit Saxena PhD , Salma K. Jabbour MD","doi":"10.1016/j.jtocrr.2024.100687","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT).</p></div><div><h3>Methods</h3><p>We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2.</p></div><div><h3>Results</h3><p>A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease > 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months.</p></div><div><h3>Conclusions</h3><p>Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 8","pages":"Article 100687"},"PeriodicalIF":3.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000572/pdfft?md5=6104558ad0c5aa0670e2088012026883&pid=1-s2.0-S2666364324000572-main.pdf","citationCount":"0","resultStr":"{\"title\":\"A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic NSCLC\",\"authors\":\"Jyoti Malhotra MD, MPH , Yong Lin PhD , Malini Patel MD , Michael J. Yellin MD , Emmanuel Zachariah PhD , Curtis Krier PhD , Ankit Saxena PhD , Salma K. Jabbour MD\",\"doi\":\"10.1016/j.jtocrr.2024.100687\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT).</p></div><div><h3>Methods</h3><p>We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2.</p></div><div><h3>Results</h3><p>A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease > 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months.</p></div><div><h3>Conclusions</h3><p>Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.</p></div>\",\"PeriodicalId\":17675,\"journal\":{\"name\":\"JTO Clinical and Research Reports\",\"volume\":\"5 8\",\"pages\":\"Article 100687\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2666364324000572/pdfft?md5=6104558ad0c5aa0670e2088012026883&pid=1-s2.0-S2666364324000572-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JTO Clinical and Research Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666364324000572\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666364324000572","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic NSCLC
Introduction
Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT).
Methods
We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2.
Results
A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease > 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months.
Conclusions
Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.