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Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer

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Abstract
Objectives: This first-in-human phase I study (NCT03179436) investigated anti-cytotoxic T-lymphocyte -associated protein 4 monoclonal antibody quavonlimab and anti-programmed death 1 monoclonal antibody pembrolizumab in patients with advanced solid tumors. The study was conducted in two parts: dose-escalation (part 1) and dose-confirmation (part 2). First-line treatment with quavonlimab + pembrolizumab conferred encouraging antitumor activity (objective response rate [ORR], 28%-40%) and was generally well tolerated (grade >= 3 treatment-related adverse events [TRAEs] were lowest with quavonlimab 25 mg every 6 weeks [Q6W] at 30% and highest with quavonlimab 75 mg Q3W at 57%) in non-small cell lung cancer. We present data from patients with extensive-stage small cell lung cancer (SCLC) receiving second-line or later therapy. Materials and Methods: Patients with stage III/IV SCLC received quavonlimab 75 mg Q6W plus pembrolizumab 200 mg Q3W for <= 2 years. Primary endpoints were safety and tolerability; ORRs as assessed by blinded independent central review per Response Evaluation Criteria In Solid Tumors v1.1 was a secondary endpoint. Progression-free survival (PFS), overall survival (OS), and the correlation of response with PD-L1 expression were exploratory endpoints. Results: Forty patients with extensive-stage SCLC received treatment; median follow-up was 13 months. Dose limiting toxicity occurred in 4 patients (10%). TRAEs occurred in 80% of patients; grade 3 events occurred in 33% of patients and no grade 4/5 events were reported. Confirmed ORRs (95% CI) were 18% (7-33) among all patients, 7% (<1-34) for PD-L1-positive tumors (n = 14), and 19% (5-42) for PD-L1-negative tumors (n = 21). Response duration ranged from 2.9 to 19.1+ months. Median PFS was 2.0 months; 6-month PFS rate was 26%. Median OS was 11.0 months; 6-month OS rate was 66%. Conclusions: Encouraging antitumor activity was observed with quavonlimab + pembrolizumab in patients with extensive-stage SCLC; responses were observed in PD-L1-positive and PD-L1-negative tumors. The combination was tolerable with manageable toxicities.
Author(s)
이대호Adnan NagrialByoung Chul ChoCorinne Maurice-DrorDavid R SpigelDong-Wan KimDrew RascoDusan KotasekJair BarJiaxin NiuKiyotaka YohMartin GutierrezMiyako SatouchiMyung-Ju AhnRachel A AlturaRuth PeretsShabana SiddiqiYixin Ren
Issued Date
2021
Type
Article
Keyword
CTLA-4 antigenDrug therapycombinationImmunotherapyLung neoplasmsProgrammed cell death 1 receptor.
DOI
10.1016/j.lungcan.2021.07.009
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8450
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2560058552&amp;context=PC&amp;vid=ULSAN&amp;lang=ko_KR&amp;search_scope=default_scope&amp;adaptor=primo_central_multiple_fe&amp;tab=default_tab&amp;query=any,contains,Anti-cytotoxic%20T-lymphocyte-associated%20antigen-4%20monoclonal%20antibody%20quavonlimab%20in%20combination%20with%20pembrolizumab:%20Safety%20and%20efficacy%20from%20a%20phase%20I%20study%20in%20previously%20treated%20extensive-stage%20small%20cell%20lung%20cancer&amp;offset=0&amp;pcAvailability=true
Publisher
LUNG CANCER
Location
아일랜드
Language
영어
ISSN
0169-5002
Citation Volume
159
Citation Number
0
Citation Start Page
162
Citation End Page
170
Appears in Collections:
Medicine > Medicine
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