A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer

被引：11

作者：

Aggarwal, Charu ^{[1
]}

Maity, Alisha P. ^{[2
]}

Bauml, Joshua M. ^{[1
,3
]}

Long, Qi ^{[1
]}

Aleman, Tomas ^{[1
]}

Ciunci, Christine ^{[1
]}

D'Avella, Christopher ^{[1
]}

Volpe, Melissa ^{[1
]}

Anderson, Evan ^{[1
]}

Jones, Lisa McCormick ^{[1
]}

Sun, Lova ^{[1
]}

Singh, Aditi P. ^{[1
]}

Marmarelis, Melina E. ^{[1
]}

Cohen, Roger B. ^{[1
]}

Langer, Corey J. ^{[1
]}

Amaravadi, Ravi ^{[1
]}

机构：

[1] Univ Penn, Dept Med, Div Hematol Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA

[2] Lankenau Med Ctr, Dept Internal Med, Wynnewood, PA USA

[3] Janssen Pharmaceut, Beerse, Belgium

来源：

ONCOLOGIST | 2023年 / 28卷 / 07期

关键词：

non-small cell lung cancer; KRAS; MEK; 1/2; inhibitor; binimetinib; hydroxychloroquine;

D O I：

10.1093/oncolo/oyad106

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: In RAS-mutant tumors, combined MEK and autophagy inhibition using chloroquine demonstrated synthetic lethality in preclinical studies. This phase II trial evaluated the safety and activity of the MEK inhibitor binimetinib combined with hydroxychloroquine (HCQ) in patients with advanced KRAS-mutant non-small cell lung cancer (NSCLC). Methods: Eligibility criteria included KRAS-mutant NSCLC, progression after first-line therapy, ECOG PS 0-1, and adequate end-organ function. Binimetinib 45 mg was administered orally (p.o.) bid with HCQ 400 mg p.o. bid. The primary endpoint was objective response rate (ORR). A Simon's 2-stage phase II clinical trial design was used, with an a error of 5% and a power beta of 80%, anticipating an ORR of 30% to proceed to the 2-stage expansion. Results: Between April 2021 and January 2022, 9 patients were enrolled to stage I: median age 64 years, 44.4% females, 78% smokers. The best response was stable disease in one patient (11.1%). The median progression free survival (PFS) was 1.9 months, and median overall survival (OS) was 5.3 months. Overall, 5 patients (55.6%) developed a grade 3 adverse event (AE). The most common grade 3 toxicity was rash (33%). Pre-specified criteria for stopping the trial early due to lack of efficacy were met. Conclusion: The combination of B + HCQ in second- or later-line treatment of patients with advanced KRAS-mutant NSCLC did not show significant antitumor activity. (ClinicalTrials.gov Identifier: NCT04735068).

引用

页码：644 / +

页数：5

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