Bemcentinib
The Food and Drug Administration (FDA) has granted fast track designation to bemcentinib, an AXL kinase inhibitor, in STK11-mutated advanced non-small-cell lung cancer.
Sunvozertinib
The FDA has granted breakthrough therapy designation for sunvozertinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, for locally advanced or metastatic non-small-cell lung cancer.
Taletrectinib
The FDA has granted breakthrough therapy designation for taletrectinib, a next-generation ROS1 inhibitor, in patients with ROS1-positive metastatic non-small-cell lung cancer.
Icotinib
Icotinib is an epidermal growth factor receptor tyrosine kinase inhibitor that is being investigated in the setting of non-small-cell lung cancer.[275]He J, Su C, Liang W, et al. Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial. Lancet Respir Med. 2021 Sep;9(9):1021-29.
http://www.ncbi.nlm.nih.gov/pubmed/34280355?tool=bestpractice.com
Ensartinib
Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase, is being investigated in the setting of non-small-cell lung cancer.[202]Cameron LB, Hitchen N, Chandran E, et al. Targeted therapy for advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer. Cochrane Database Syst Rev. 2022 Jan 7;1(1):CD013453.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013453.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/34994987?tool=bestpractice.com
[276]Horn L, Wang Z, Wu G, et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: a randomized clinical trial. JAMA Oncol. 2021 Nov 1;7(11):1617-25.
https://www.doi.org/10.1001/jamaoncol.2021.3523
http://www.ncbi.nlm.nih.gov/pubmed/34473194?tool=bestpractice.com
Sugemalimab
Sugemalimab is a programmed death-ligand 1 (PD-L1) inhibitor that is being investigated in the setting of non-small-cell lung cancer.[277]Zhou Q, Chen M, Jiang O, et al. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):209-19.
http://www.ncbi.nlm.nih.gov/pubmed/35038429?tool=bestpractice.com
Aumolertinib
Aumolertinib is an epidermal growth factor receptor tyrosine kinase inhibitor that is being investigated in the setting of non-small-cell lung cancer.[278]Lu S, Dong X, Jian H, et al. AENEAS: a randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non-small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol. 2022 Sep 20;40(27):3162-71.
https://www.doi.org/10.1200/JCO.21.02641
http://www.ncbi.nlm.nih.gov/pubmed/35580297?tool=bestpractice.com
Eftilagimod alpha
The FDA has granted breakthrough therapy designation for eftilagimod alpha, a soluble LAG-3 fusion protein, in combination with pembrolizumab in first-line treatment of stage IIIB/IV non-small-cell lung cancer patients expressing PD-L1 status ≥1%, not amenable to epidermal growth factor receptor/ALK-based therapy. A phase 2 trial is ongoing.[279]ClinicalTrials.gov. Combination study with soluble LAG-3 fusion protein eftilagimod alpha (IMP321) and pembrolizumab in patients with previously untreated unresectable or metastatic NSCLC, or recurrent PD-X refractory NSCLC or with recurrent or metastatic HNSCC (TACTI-002). 2023 [internet publication].
https://clinicaltrials.gov/study/NCT03625323
Vebreltinib
Vebreltinib is a highly selective ATP-competitive small-molecule MET inhibitor. The FDA has granted orphan designation to vebreltinib for the treatment of non-small-cell lung cancer with MET genomic tumor aberrations. A phase 2 trial is ongoing.[280]ClinicalTrials.gov. APL-101 study of subjects with NSCLC with c-met EXON 14 skip mutations and c-met dysregulation advanced solid tumors (SPARTA). 2024 [internet publication].
https://clinicaltrials.gov/study/NCT03175224
Furmonertinib
Furmonertinib is an epidermal growth factor receptor tyrosine kinase inhibitor that is being investigated in the setting of non-small-cell lung cancer.[281]Shi Y, Chen G, Wang X, et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med. 2022 Nov;10(11):1019-28.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00168-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35662408?tool=bestpractice.com
Sintilimab
Sintilimab, an anti-PD-1 monoclonal antibody, is being investigated in the setting of non-small-cell lung cancer.[282]Lu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Sep;23(9):1167-79.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00382-5/abstract
http://www.ncbi.nlm.nih.gov/pubmed/35908558?tool=bestpractice.com
Toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody that is being investigated in the setting of non-small-cell lung cancer.[283]Wang Z, Wu L, Li B, et al. Toripalimab plus chemotherapy for patients with treatment-naive advanced non-small-cell lung cancer: a multicenter randomized phase III trial (CHOICE-01). J Clin Oncol. 2023 Jan 20;41(3):651-63.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870236
http://www.ncbi.nlm.nih.gov/pubmed/36206498?tool=bestpractice.com
Iruplinakib
Iruplinakib is an ALK tyrosine kinase inhibitor that is being investigated in the setting of non-small-cell lung cancer.[284]Shi Y, Chen J, Yang R, et al. Iruplinalkib (WX-0593) versus crizotinib in ALK TKI-naive locally advanced or metastatic ALK-positive NSCLC: interim analysis of a randomized, open-label, phase 3 study (INSPIRE). J Thorac Oncol. 2024 Jan 25;S1556-0864(24)00033-9.
https://www.doi.org/10.1016/j.jtho.2024.01.013
http://www.ncbi.nlm.nih.gov/pubmed/38280448?tool=bestpractice.com
Penpulimab
Penpulimab is a programmed death (PD)-1 inhibitor that is being investigated in the setting of advanced squamous non-small-cell lung cancer.[285]Zhong H, Sun S, Chen J, et al. First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial. Lancet Respir Med. 2024 May;12(5):355-65.
http://www.ncbi.nlm.nih.gov/pubmed/38309287?tool=bestpractice.com