Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with Stage IV non-small cell lung cancer. (April 2020)

• Record Type: Journal Article
• Authors: Besse, Benjamin; Garrido, Pilar; Cortot, Alexis B.; Johnson, Melissa; Murakami, Haruyasu; Gazzah, Anas; Gil, Maciej; Bennouna, Jaafar
• Is Part Of: Lung cancer. Volume 142(2020)
• Page Start: 63
• Page End: 69
• Publication Date: 2020-04
• Subjects: AE adverse event -- AESI adverse events of special interest -- ALK anaplastic lymphoma kinase -- CI confidence interval -- CR complete response -- DCR disease control rate -- DLT dose-limiting toxicity -- DoR duration of response -- ECOG Eastern Cooperative Oncology Group -- EGFR epidermal growth factor receptor -- FISH fluorescence in situ hybridization -- IgG1 immunoglobulin G, subclass 1 -- IgG4 immunoglobulin G, subclass 4 -- IHC immunohistochemistry -- IV intravenous -- mAb monoclonal antibody -- mPFS median progression-free survival -- MTD maximum tolerated dose -- NSCLC non-small cell lung cancer -- ORR overall response rate -- OS overall survival -- PD-1 programmed cell death protein 1 -- PD-L1 programmed death-ligand 1 -- PD-L2 programmed death-ligand 2 -- PFS progression-free survival -- PR partial response -- Q3W every 3 weeks -- TEAE treatment-emergent adverse event -- TKI tyrosine kinase inhibitor; EGFR inhibitor -- Immune checkpoint inhibitor -- Advanced non-small cell lung cancer -- Necitumumab -- Pembrolizumab; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.02.003
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Efficacy and safety of necitumumab combined with pembrolizumab was assessed in advanced NSCLC. Pretreated NSCLC population had relatively high proportion of PDL1 negative patients. Modest benefits of combined necitumumab and pembrolizumab seen in patients with NSCLC. Safety corresponded to individual profiles of both drugs, with no additive toxicities. Abstract: Objectives: Efficacy and safety of necitumumab when combined with pembrolizumab was assessed in patients with Stage IV non-small cell lung cancer (NSCLC) of squamous and nonsquamous histology, who had progressed after treatment with a platinum-based doublet. Materials and methods: This single-arm, multicenter, phase Ib study had a dose-finding phase, in which escalating doses of necitumumab (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembrolizumab (200 mg IV) on Day 1 Q3W, and expansion cohorts. Patients were treated until progressive disease (PD), toxicity requiring cessation, protocol noncompliance, or withdrawal of consent. Efficacy was evaluated by overall response rate (ORR). Results: In 64 treated patients (32 patients [50 %] were programmed death-ligand 1 [PD-L1] negative), confirmed ORR was 23.4 % (95 % confidence interval [CI] 13.8 %–35.7 %). Two patients (3.1 %) had complete response (CR), 13 patients (20.3 %) had partial response (PR), 26 patients (40.6 %) had stable disease, 17 patients (26.6 %) had PD, and 6 patients (9.4 %) were not evaluable. Regardless of histology or PD-L1 status, median PFS (mPFS) was 4.1 months (95 % CI 2.4–6.9 months) and OS at 6 months was 74.7 % (61.5%–83.9%). Confirmed disease control rate was 64.1 % (95 % CI 51.5–75.7). Patients with programmed death-ligand 1 (PD-L1) ≥1% had numerically improved ORR and median progression-free survival when compared with patients with PD-L1 negative cancer. No dose-limiting toxicities were recorded and the combination of necitumumab 800 mg with pembrolizumab 200 mg was considered tolerable. Conclusion: Results suggest modest benefits of second-line necitumumab and pembrolizumab combination therapy in patients with Stage IV NSCLC. Safety profiles were consistent with class effects typical of epidermal growth factor receptor inhibitors and immunotherapies with no additive toxicities.