Skip to main content
. 2021 Dec 14;2(4):692–729. doi: 10.1002/mco2.105

TABLE 1.

Targeted therapy in driver gene‐positive advanced NSCLC patients

Target Inhibitor Indications Status Company Key clinical trials
EGFR (first generation)
†Geftinib (Iressa) Advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R mutations FDA, Jul 2015 (first line) AstraZeneca IPASS, NCT00322452 54
Erlotinib (Tarceva) Advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R mutations FDA, Nov 2013 (first line) Genentech OPTIMAL, NCT00874419 55
Icotinib (Conmana) Advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R mutations NMPA, Nov 2014 (first line) Beta Pharma ICOGEN, NCT01040780 56
EGFR (second generation)
†Afatinib (Gilotrif) Advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R mutations FDA, Jul 2013 (first line) Boehringer Ingelheim LUX‐Lung 2, NCT00525148 57 ; LUX‐Lung 3, NCT00949650 58 ; LUX‐Lung 6, NCT01121393 59
†Dacomitinib (Vizimpro) Advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R mutations FDA, Nov 2015 (first line) Pfizer ARCHER 1050, NCT01774721 60
EGFR (third generation)
†Osimertinib (Tagrisso)

  1. Advanced NSCLC with EGFR T790M mutation

  2. Advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R mutations

  1. FDA, Nov 2015 (first line)

  2. FDA, Dec 2020 (first line)

 AstraZeneca FLAURA, NCT02296125 61 ; ADAURA, NCT02511106 62
Aulmonertinib (Ameile) Advance NSCLC patients with EGFR T790M, who got disease progression on or after EGFR TKI therapy NMPA, Mar 2020 (second line) EQRx and Hansoh Pharma APOLLO, NCT02981108 63
Furmonertinib (Alflutinib) Advance NSCLC patients with EGFR T790M, who got disease progression on or after EGFR TKI therapy NMPA, Mar 2020 (second line) Shanghai Allist Pharmaceuticals ALSC003, NCT03452592 64
Anti‐EGFR antibody
Necitumumab (Portrazza)

  1. In combination with pemetrexed and cisplatin, for patients with metastatic nonsquamous NSCLC

  2. In combination with gemcitabine and cisplatin, for patients with metastatic squamous NSCLC

  1. FDA, Nov 2014 (first line)

  2. FDA, Nov 2015 (first line)

 Eli Lilly

  1. INSPIRE, NCT00982111 65

  2. SQUIRE, NCT00981058 66

EGFR (exon 20 insertion)
Amivantamab‐vmjw (Rybrevant) Advanced exon 20 insertion‐positive NSCLC patients progressed after platinum‐based chemotherapy FDA, May 2021 (second line) Janssen Biotech CHRYSALIS, NCT02609776 67
Mobocertinib (Exkivity) Advanced exon 20 insertion‐positive NSCLC patients progressed after platinum‐based chemotherapy FDA, Sep 2021 (second line) Takeda Pharmaceuticals Study 101, NCT02716116 68
ALK
†Crizotinib (Xalkori) Advanced NSCLC with ALK rearrangement FDA, Aug 2011 (first line) Pfizer

PROFILE 1001, NCT00585195 69 ;

PROFILE 1005, NCT00932451 70

†Ceritinib (Zykadia) Advanced NSCLC patients with ALK arrangements FDA, May 2017 (first line) Novartis ASCEND‐4, NCT01828099 71
†Alectinib (Alecensa) Advanced NSCLC patients with ALK arrangements FDA, Nov 2017 (first line) Hoffmann‐La Roche and Genentech

ALUR, NCT02604342 72 ;

ALEX, NCT02075840 73

†Brigatinib (Alunbrig) Advanced NSCLC patients with ALK arrangements FDA, May 2020 (first line) ARIAD ALTA 1L, NCT02737501 74
†Lorlatinib (Lorbrena) Advanced NSCLC patients with ALK arrangements FDA, Mar 2021 (first line) Pfizer Study B7461001, NCT01970865 75 ; Study B7461006, NCT03052608 76
ROS1
†Crizotinib (Xalkori) Advance ROS1‐positive NSCLC FDA, Mar 2016 (first line) Pfizer PROFILE 1001, NCT00585195 69
†Entrectinib (Rozlytrek) Advance ROS1‐positive NSCLC FDA, Aug 2019 (first line) Genentech

STARTRK‐1, NCT02097810; STARTRK‐2, NCT02568267;

ALKA‐372‐001, EudraCT number, 2012‐000148‐88 77

BRAF
†Dabrafenib (Tafinlar) In combination with trametinib for advance BRAF V600E‐positive NSCLC FDA, Jun 2017 (first line) Novartis BRF113928, NCT01336634 78
KRAS
Sotorasib (Lumakras) KRAS G12C‐mutated advanced NSCLC who have received at least one prior systemic therapy FDA, May 2021 (second line) Amgen CodeBreaK 100, NCT03600883 79
RET
†Selpercatinib (Retevmo) Advanced RET fusion‐positive NSCLC FDA, May 2020 (first line) Eli Lilly LIBRETTO‐001, NCT03157128 80
†Pralsetinib (Gavretotm) Advanced RET fusion‐positive NSCLC FDA, Sep 2020 (first line) Blueprint Medicines Corporation ARROW, NCT03037385 81
MET
†Capmatinib (Tabrecta) Advanced NSCLC patients with MET exon 14 skipping alterations FDA, May 2020 (first line) Novartis GEOMETRY mono‐1 trial, NCT02414139 82
†Tepotinib (Tepmetko) Advanced NSCLC patients with MET exon 14 skipping alterations FDA, Feb 2021 (first line) Merck KGaA V ISION, NCT02864992 83
Crizotinib (Xalkori) Advanced MET exon 14 skipping‐positive NSCLC patients progressed after platinum‐based chemotherapy FDA, May 2018 (second line) Pfizer PROFILE 1001 study, NCT00585195 69
Savolitinib (Orpathys) Advanced NSCLC patients with MET exon 14 skipping alterations who have progressed after or who are unable to tolerate platinum‐based chemotherapy NMPA, Jun 2021 (second line) HUTCHMED and AstraZeneca NCT02897479 84
NTRK 1/2/3
†Entrectinib (Rozlytrek) Solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation FDA, Aug 2019 (second line) Genentech Inc

STARTRK‐1, NCT02097810; STARTRK‐2, NCT02568267;

ALKA‐372‐001, EudraCT number, 2012‐000148‐88 85

†Larotrectinib (VITRAKVI) Solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation FDA, Nov 2018 (second line) Loxo Oncology Inc. and Bayer LOXO‐TRK‐14001, NCT02122913 86 ; SCOUT, NCT02637687 87 ; NAVIGATE, NCT02576431 88
Repotrectinib (TPX‐0005) Solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation FDA, Oct 2021 (second line) Turning Point Therapeutics, Inc TRIDENT‐1, NCT03093116 89

Note: Inhibitors with † are recommended as first‐line treatment for advanced NSCLC with corresponding mutations, according to the NCCN guideline 2021.

Abbreviations: FDA, the U.S. Food and Drug administration; NMPA, Chinese National Medical Products Administration.