Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma

被引：4

作者：

Hamid, Omid ^{[1
]}

Lewis, Karl D. ^{[2
]}

Weise, Amy ^{[3
]}

McKean, Meredith ^{[4
,5
]}

Papadopoulos, Kyriakos P. ^{[6
]}

Crown, John ^{[7
]}

Kim, Tae Min ^{[8
]}

Lee, Dae Ho ^{[9
]}

Thomas, Sajeve S. ^{[10
]}

Mehnert, Janice ^{[11
]}

Kaczmar, John ^{[12
]}

Lakhani, Nehal J. ^{[13
]}

Kim, Kevin B. ^{[14
]}

Middleton, Mark R. ^{[15
]}

Rabinowits, Guilherme ^{[16
]}

Spira, Alexander I. ^{[17
,18
]}

Yushak, Melinda ^{[19
]}

Mehmi, Inderjit ^{[1
]}

Fang, Fang ^{[20
]}

Chen, Shuquan ^{[20
]}

Mani, Jayakumar ^{[20
]}

Jankovic, Vladimir ^{[20
]}

Wang, Fang ^{[20
]}

Fiaschi, Nathalie ^{[20
]}

Brennan, Laura ^{[20
]}

Paccaly, Anne ^{[20
]}

Masinde, Sheila ^{[20
]}

Salvati, Mark ^{[20
]}

Fury, Matthew G. ^{[20
]}

Kroog, Glenn ^{[20
]}

Lowy, Israel ^{[20
]}

Gullo, Giuseppe ^{[20
]}

机构：

[1] Angeles Clin & Res Inst Cedars Sinai Affiliate, Los Angeles, CA 90025 USA

[2] Univ Colorado, Denver Canc Ctr, Aurora, CO USA

[3] Henry Ford Hosp, Detroit, MI USA

[4] Sarah Cannon Res Inst, Nashville, TN USA

[5] Tennessee Oncol PLLC, Nashville, TN USA

[6] START, San Antonio, TX USA

[7] St Vincents Univ Hosp, Dublin, Ireland

[8] Seoul Natl Univ Hosp, Seoul, South Korea

[9] Asan Med Ctr, Seoul, South Korea

[10] Univ Florida, Hlth Canc Ctr, Orlando Hlth, Orlando, FL USA

[11] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA

[12] MUSC Hollings Canc Ctr, Charleston, SC USA

[13] START Midwest, Grand Rapids, MI USA

[14] Calif Pacific Med Ctr Res Inst, Ctr Melanoma Res & Treatment, San Francisco, CA USA

[15] NIHR Biomed Res Ctr, Dept Oncol, Oxford, England

[16] Baptist Hlth South Florida, Miami Canc Inst, Miami, FL USA

[17] Virginia Canc Specialists, Fairfax, VA USA

[18] US Oncol Res, Fairfax, VA USA

[19] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA USA

[20] Regeneron Pharmaceut Inc, Tarrytown, NY USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2024年 / 42卷 / 24期

关键词：

PEMBROLIZUMAB; THERAPY; IPILIMUMAB; EXPRESSION; NIVOLUMAB;

D O I：

10.1200/JCO.23.02172

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSECoblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma.METHODSPatients with advanced melanoma were eligible for enrollment into four cohorts: three for patients without and one for patients with previous anti-PD-1 therapy in the advanced disease setting. Patients were treated with fianlimab 1,600 mg and cemiplimab 350 mg intravenously once every 3 weeks for up to 51 weeks, with an optional additional 51 weeks if clinically indicated. The primary end point was objective response rate (ORR) per RECIST 1.1 criteria.RESULTSORRs were 63% for patients with anti-PD-1-na & iuml;ve melanoma (cohort-6; n = 40; median follow-up 20.8 months), 63% for patients with systemic treatment-na & iuml;ve melanoma (cohort-15; n = 40; 11.5 months), and 56% for patients with previous neo/adjuvant treatment melanoma (cohort-16; n = 18, 9.7 months). At a median follow-up of 12.6 months for the combined cohorts (6 + 15 + 16), the ORR was 61.2% and the median progression-free survival (mPFS) 13.3 months (95% CI, 7.5 to not estimated [NE]). In patients (n = 13) with previous anti-PD-1 adjuvant therapy, ORR was 61.5% and mPFS 12 months (95% CI, 1.4 to NE). ORR in patients with previous anti-PD-1 therapy for advanced disease (n = 15) was 13.3% and mPFS 1.5 months (95% CI, 1.3 to 7.7). Treatment-emergent and treatment-related adverse events >= grade 3 (G3) were observed in 44% and 22% of patients, respectively. Except for increased incidence of adrenal insufficiency (12%-G1-4, 4%-G3-4), no new safety signals were recorded.CONCLUSIONThe current results show a promising benefit-risk profile of fianlimab/cemiplimab combination for patients with advanced melanoma, including those with previous anti-PD-1 therapy in the adjuvant, but not advanced, setting.

引用

页码：2928 / 2938

页数：14