Sunvozertinib
The US Food and Drug Administration (FDA) has approved sunvozertinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, for locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 mutations, whose disease has progressed after platinum-based chemotherapy.
Datopotamab deruxtecan
The FDA has granted accelerated approval to datopotamab deruxtecan, a trop-2-directed monoclonal antibody and topoisomerase inhibitor conjugate, for locally advanced or metastatic EGFR-mutated non-small cell lung cancer in patients who have previously received EGFR-directed therapy and platinum-based chemotherapy. The approval was based on pooled data from two trials that reported an objective response rate of 43%, and a median duration of response of 7 months.[282]Ahn MJ, Lisberg A, Goto Y, et al. A pooled analysis of datopotamab deruxtecan in patients with EGFR-mutated NSCLC. J Thorac Oncol. 2025 Jun 12:S1556-0864(25)00761-0.
https://www.jto.org/article/S1556-0864(25)00761-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/40516821?tool=bestpractice.com
Icotinib
Icotinib is an EGFR tyrosine kinase inhibitor that is being investigated in the setting of non-small cell lung cancer.[283]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
Sugemalimab
Sugemalimab is a programmed death-ligand 1 (PD-L1) inhibitor that is being investigated in the setting of non-small cell lung cancer.[284]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
[285]Zhou C, Wang Z, Sun M, et al. Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC. Nat Cancer. 2023 Jun;4(6):860-71.
http://www.ncbi.nlm.nih.gov/pubmed/37322367?tool=bestpractice.com
Aumolertinib
Aumolertinib is an EGFR tyrosine kinase inhibitor that is being investigated in the setting of non-small cell lung cancer.[286]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
[287]Lu S, Dong X, Jian H, et al. Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, EGFR-mutated, advanced non-small cell lung cancer: data from a randomized phase III trial (AENEAS). Cancer Commun (Lond). 2024 Sep;44(9):1005-17.
https://onlinelibrary.wiley.com/doi/10.1002/cac2.12594
http://www.ncbi.nlm.nih.gov/pubmed/39016053?tool=bestpractice.com
Eftilagimod alpha
Eftilagimod alpha (a soluble LAG-3 fusion protein), in combination with pembrolizumab and chemotherapy, is being investigated in a phase 3 trial for the treatment of metastatic NSCLC.[288]ClinicalTrials.gov. Study of eftilagimod alfa (Efti) in combination with pembrolizumab and chemotherapy versus placebo in combination with pembrolizumab and chemotherapy in participants with metastatic non-small cell lung cancer (NSCLC) (TACTI-004). Oct 2025 [internet publication].
https://clinicaltrials.gov/study/NCT06726265
The FDA has granted fast-track designation to eftilagimod alpha for the first-line treatment of non-small cell lung cancer.
Vebreltinib
Vebreltinib is a highly selective ATP-competitive small-molecule MET inhibitor. The US FDA has granted orphan designation to vebreltinib for the treatment of non-small cell lung cancer with MET genomic tumour aberrations. A phase 2 trial is ongoing.[289]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 EGFR tyrosine kinase inhibitor. The FDA has granted orphan drug designation to furmonertinib for the treatment of non-small cell lung cancer with EGFR mutations or HER2 or HER4 mutations.[290]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.[291]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.[292]Lu S, Zhang W, Wu L, et al. Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: the neotorch randomized clinical trial. JAMA. 2024 Jan 16;331(3):201-11.
https://jamanetwork.com/journals/jama/fullarticle/2813880
http://www.ncbi.nlm.nih.gov/pubmed/38227033?tool=bestpractice.com
[293]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
Iruplinalkib
Iruplinalkib is an ALK tyrosine kinase inhibitor that is being investigated in the setting of non-small cell lung cancer.[294]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.jto.org/article/S1556-0864(24)00033-9/fulltext
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.[295]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