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Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer
DC Field | Value | Language |
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dc.contributor.author | 조병철 | - |
dc.date.accessioned | 2022-01-26T01:58:30Z | - |
dc.date.available | 2022-01-26T01:58:30Z | - |
dc.date.issued | 2021-03 | - |
dc.identifier.issn | 0923-7534 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/187419 | - |
dc.description.abstract | Background: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. Patients and methods: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints. Results: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. Conclusions: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Oxford University Press | - |
dc.relation.isPartOf | ANNALS OF ONCOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Antibodies, Monoclonal, Humanized / adverse effects | - |
dc.subject.MESH | Antineoplastic Combined Chemotherapy Protocols / adverse effects | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / drug therapy | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lung Neoplasms* / drug therapy | - |
dc.title | Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | R Perets | - |
dc.contributor.googleauthor | J Bar | - |
dc.contributor.googleauthor | D W Rasco | - |
dc.contributor.googleauthor | M-J Ahn | - |
dc.contributor.googleauthor | K Yoh | - |
dc.contributor.googleauthor | D-W Kim | - |
dc.contributor.googleauthor | A Nagrial | - |
dc.contributor.googleauthor | M Satouchi | - |
dc.contributor.googleauthor | D H Lee | - |
dc.contributor.googleauthor | D R Spigel | - |
dc.contributor.googleauthor | D Kotasek | - |
dc.contributor.googleauthor | M Gutierrez | - |
dc.contributor.googleauthor | J Niu | - |
dc.contributor.googleauthor | S Siddiqi | - |
dc.contributor.googleauthor | X Li | - |
dc.contributor.googleauthor | J Cyrus | - |
dc.contributor.googleauthor | A Chackerian | - |
dc.contributor.googleauthor | A Chain | - |
dc.contributor.googleauthor | R A Altura | - |
dc.contributor.googleauthor | B C Cho | - |
dc.identifier.doi | 10.1016/j.annonc.2020.11.020 | - |
dc.contributor.localId | A03822 | - |
dc.relation.journalcode | J00171 | - |
dc.identifier.eissn | 1569-8041 | - |
dc.identifier.pmid | 33276076 | - |
dc.subject.keyword | CTLA-4 | - |
dc.subject.keyword | MK-1308 | - |
dc.subject.keyword | immunotherapy | - |
dc.subject.keyword | non-small-cell lung cancer | - |
dc.subject.keyword | pembrolizumab | - |
dc.subject.keyword | quavonlimab | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.citation.volume | 32 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 395 | - |
dc.citation.endPage | 403 | - |
dc.identifier.bibliographicCitation | ANNALS OF ONCOLOGY, Vol.32(3) : 395-403, 2021-03 | - |
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