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

被引：65

作者：

Perets, R. ^{[1
]}

Bar, J. ^{[2
,3
]}

Rasco, D. W. ^{[4
]}

Ahn, M-J ^{[5
]}

Yoh, K. ^{[6
]}

Kim, D-W ^{[7
,8
]}

Nagrial, A. ^{[9
,10
]}

Satouchi, M. ^{[11
]}

Lee, D. H. ^{[12
]}

Spigel, D. R. ^{[13
]}

Kotasek, D. ^{[14
,15
]}

Gutierrez, M. ^{[16
]}

Niu, J. ^{[17
]}

Siddiqi, S. ^{[18
]}

Li, X. ^{[18
]}

Cyrus, J. ^{[18
]}

Chackerian, A. ^{[19
]}

Chain, A. ^{[18
]}

Altura, R. A. ^{[18
]}

Cho, B. C. ^{[20
]}

机构：

[1] Technion Israel Inst Technol, Rambam Med Ctr, Dept Oncol, Haifa, Israel

[2] Chaim Sheba Med Ctr Tel HaShomer, Canc Ctr, Ramat Gan, Israel

[3] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[4] START, Phase 1, San Antonio, TX USA

[5] Sungkyunkwan Univ Med, Samsung Med Ctr, Dept Med, Seoul, South Korea

[6] Natl Canc Ctr Hosp East, Dept Thorac Oncol, Kashiwa, Chiba, Japan

[7] Seoul Natl Univ Hosp, Med Oncol Ctr, Dept Hemato Oncol, Seoul, South Korea

[8] Seoul Natl Univ Hosp, Personalized Canc Med Ctr, Seoul, South Korea

[9] Blacktown Hosp, Dept Canc & Hematol, Sydney, NSW, Australia

[10] Univ Sydney, Sydney, NSW, Australia

[11] Hyogo Canc Ctr, Dept Thorac Oncol, Akashi, Hyogo, Japan

[12] Univ Ulsan, Asan Med Ctr, Dept Oncol, Coll Med, Seoul, South Korea

[13] Tennessee Oncol PLLC, Dept Med Oncol, Sarah Cannon Res Inst, Nashville, TN USA

[14] Adelaide Canc Ctr, Dept Med Oncol, Kurralta Pk, Australia

[15] Univ Adelaide, Kurralta Pk, Australia

[16] Hackensack Univ, Dept Hematol Hematol Oncol & Med Oncol, Med Ctr, Hackensack, NJ USA

[17] Banner MD Anderson Canc Ctr, Dept Med Oncol, Gilbert, AZ USA

[18] Merck & Co Inc, MRL, Kenilworth, NJ USA

[19] Merck & Co Inc, Dept Discovery Oncol, Kenilworth, NJ USA

[20] Yonsei Canc Ctr, Div Med Oncol, Seoul, South Korea

来源：

ANNALS OF ONCOLOGY | 2021年 / 32卷 / 03期

关键词：

non-small-cell lung cancer; quavonlimab; MK-1308; CTLA-4; pembrolizumab; immunotherapy; NIVOLUMAB PLUS IPILIMUMAB; OPEN-LABEL; BLOCKADE;

D O I：

10.1016/j.annonc.2020.11.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 H 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 (a), 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% a, 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.

引用

页码：395 / 403

页数：9

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