What changed: Non-small-cell lung cancer

FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer

When this page itself was last checked or edited.

ROS1+ NSCLC (ARROS-1)

First-line HER2-mutant non-squamous NSCLC

BLA submitted by Summit for EGFR-mutant NSCLC after TKI (HARMONi)

Aumseqa: first-line advanced NSCLC with EGFR exon 19 deletion or L858R; advanced EGFR T790M-positive NSCLC

ROS1+ NSCLC (July 2026)

First-line HER2-mutant non-squamous NSCLC

Interim PFS not statistically significant (May 2026); final readouts pending.

Superior PFS and OS vs approved G12C inhibitors (topline, July 2026).

A milestone in how this cancer is treated.

Subcutaneous formulation (PALOMA-3)

Accelerated approval, previously treated HER2-mutant non-squamous NSCLC (Beamion LUNG-1)

EGFR-mutant NSCLC after TKI and platinum chemotherapy (accelerated)

Full approval in NSCLC (KRYSTAL-12)

Accelerated approval, previously treated c-MET-high non-squamous NSCLC (LUMINOSITY)

HER2-mutant NSCLC

First-line PD-L1+ NSCLC (HARMONi-2)

EGFR-mutant NSCLC after TKI failure

EGFR-mutant NSCLC after EGFR TKI and platinum chemotherapy

1L EGFR-mutant NSCLC with amivantamab; 20 Jan 2025

ROS1+ NSCLC; NTRK+ solid tumours; 13 Jan 2025 (conditional)

With osimertinib in EGFR-mutant NSCLC with MET amplification after EGFR TKI (SACHI)

HER2 TKD-mutant non-squamous NSCLC after prior systemic therapy (accelerated)

Locally advanced/metastatic NSCLC with EGFR exon 20 insertions after platinum

ROS1-positive NSCLC

Locally advanced or metastatic ROS1-positive NSCLC

c-MET-high non-squamous NSCLC, previously treated (accelerated)

HER2-mutant NSCLC after ≥1 systemic therapy (May 2025)

HER2-mutant NSCLC, previously treated (accelerated)

ORR 31% in heavily pretreated ALK+ NSCLC; NDA under priority review.

PFS HR 0.

ORR ~64%; accelerated approval Nov 2025.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

Accelerated approval, NRG1-fusion NSCLC and pancreatic adenocarcinoma (eNRGy): first therapy for NRG1 fusions

Breakthrough Therapy designation, EGFR-mutant NSCLC after TKI

Optune Lua, metastatic NSCLC after platinum (LUNAR)

Unresectable stage III after chemoradiation (LAURA)

After osimertinib, with chemotherapy (MARIPOSA-2)

First-line EGFR-mutant NSCLC with lazertinib (MARIPOSA)

Breakthrough Therapy designation, ROS1+ NSCLC after prior ROS1 TKI

EGFR-mutant NSCLC after TKI, with chemotherapy (HARMONi-A)

First-line exon 20 insertion with chemotherapy (PAPILLON)

Breakthrough Therapy designation

First-line with chemotherapy (FLAURA2)

KRAS G12C NSCLC after ≥1 line; 5 Jan 2024 (conditional)

Adjuvant ALK+ NSCLC after resection (stage IB ≥4 cm to IIIA)

First-line EGFR-mutant NSCLC with lazertinib

ALK-positive locally advanced or metastatic NSCLC, ALK-inhibitor-naive

KRAS G12C-mutant advanced NSCLC after at least one systemic therapy

KRAS G12C-mutant advanced NSCLC after at least one systemic therapy

KRAS G12C-mutant advanced non-small cell lung cancer after prior systemic therapy

EGFR-mutant NSCLC after TKI (with chemotherapy); first-line PD-L1+ NSCLC

First-line EGFR exon 19 del / L858R NSCLC with amivantamab

Locally advanced or metastatic EGFR T790M-mutant non-small cell lung cancer after prior EGFR inhibitor therapy

Metastatic NSCLC after platinum with PD-1 or docetaxel

NTRK-fusion solid tumours (tumour-agnostic)

Pretreated advanced TNBC; later EGFR-mutant NSCLC after TKI

First-line metastatic NSCLC with platinum chemotherapy, no sensitising EGFR, ALK, ROS1 or RET alterations

NRG1-fusion NSCLC and pancreatic adenocarcinoma

PFS HR 0.

PFS 7.

PFS HR 0.

PFS HR 0.

ORR 28.

Placebo-adjusted weight gain 2.

A milestone in how this cancer is treated.

Perioperative NSCLC (KEYNOTE-671)

BRAF V600E NSCLC with binimetinib

BRAF V600E metastatic NSCLC with encorafenib

ALK-positive non-small-cell lung cancer after crizotinib; first line from 2024

ROS1+ locally advanced or metastatic NSCLC

EGFR exon 20 insertion NSCLC after platinum

DFS HR 0.

PFS HR 0.

EFS HR 0.

PFS HR 0.

Weight gain over 5%: 60% vs 9%; appetite improvement 43% vs 13%.

PFS HR 0.

PFS HR 0.

ORR 43.

A milestone in how this cancer is treated.

Accelerated approval, KRAS G12C NSCLC after ≥1 therapy

RET-fusion solid tumours (tumour-agnostic, accelerated); full approval in NSCLC

HER2-mutant NSCLC (accelerated)

Neoadjuvant NSCLC with chemotherapy (CheckMate 816)

Complete response letter for ORIENT-11 (first-line non-squamous NSCLC); ODAC voted 14 to 1 that additional data were needed for US applicability

Breakthrough Therapy designation, c-MET overexpressing NSCLC

KRAS G12C NSCLC (accelerated)

Tepmetko 2022; Tabrecta 2022

First-line EGFR exon 19 deletion or L858R NSCLC (FURLONG)

Companion diagnostic for adagrasib in KRAS G12C-mutant NSCLC (plasma)

Unresectable stage III NSCLC without progression after chemoradiotherapy (GEMSTONE-301)

Advanced NSCLC with MET exon 14 skipping alterations after immunotherapy or platinum chemotherapy

HER2-low metastatic breast cancer; HER2-mutant NSCLC

Metastatic NSCLC without EGFR/ALK, with durvalumab and platinum chemotherapy; unresectable HCC with durvalumab

PFS 19.

EFS HR 0.

PFS HR 0.

PFS 20.

PFS 7.

Median overall survival 14.

A milestone in how this cancer is treated.

Breakthrough Therapy designation, EGFR-mutant NSCLC after TKI and platinum

Adjuvant NSCLC, PD-L1 ≥1% (IMpower010)

Accelerated approval, KRAS G12C NSCLC after ≥1 therapy: first KRAS inhibitor

Accelerated approval, EGFR exon 20 insertion NSCLC after platinum

First-line ALK+ NSCLC (CROWN); full approval

First-line PD-L1 ≥50% NSCLC (EMPOWER-Lung 1)

Exon 20; 1L with lazertinib Jan 2025

EGFR exon 20 insertion NSCLC

First-line EGFR exon 19 deletion or L858R NSCLC (AENEAS)

EGFR T790M-positive locally advanced or metastatic NSCLC after EGFR TKI therapy

Adjuvant treatment of resected stage II to IIIA EGFR-mutant NSCLC (EVIDENCE)

First-line ALK+ NSCLC

EGFR exon 20 insertion NSCLC after platinum

510(k) clearance: AI decision support for indeterminate pulmonary nodules

MET exon 14 skipping NSCLC after platinum chemotherapy or unfit for chemotherapy (conditional; later full)

First-line non-squamous NSCLC with pemetrexed and platinum (ORIENT-11); first-line squamous NSCLC with gemcitabine and platinum (ORIENT-12); first-line unresectable hepatocellular carcinoma with IBI305 (ORIENT-32)

KRAS G12C NSCLC, previously treated (accelerated)

First-line metastatic squamous and non-squamous NSCLC with platinum chemotherapy (GEMSTONE-302)

Metastatic NSCLC with MET exon 14 skipping alterations

Companion diagnostic for adjuvant atezolizumab in PD-L1 TC ≥1% resected NSCLC

PFS 11.

Nivolumab plus ipilimumab did not improve survival over nivolumab alone; the trial closed for futility.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

Adjuvant EGFR-mutant NSCLC after resection (ADAURA)

With nivolumab in first-line NSCLC (CheckMate 227) and HCC

Accelerated approval, RET-fusion NSCLC and thyroid cancer, RET-mutant MTC (LIBRETTO-001)

EGFR T790M-positive locally advanced or metastatic NSCLC after EGFR TKI therapy

First-line ALK-positive metastatic NSCLC

MET exon 14 skipping NSCLC (capmatinib; tepotinib 2021)

Metastatic NSCLC with a MET exon 14 skipping mutation (accelerated approval)

ALK-positive NSCLC after crizotinib

Companion diagnostic for osimertinib (EGFR) in NSCLC; first liquid comprehensive genomic profiling test

CE mark

Adjuvant EGFR-mutant NSCLC

RET-fusion metastatic NSCLC (full approval 2023)

RET-fusion NSCLC and thyroid; RET-mutant MTC

Unresectable advanced or recurrent NSCLC with MET exon 14 skipping

OS HR 0.

5-year PFS 60% vs 8%, HR 0.

PFS 16 vs 8 months (HR 0.

Genotype-matched targeted arms (taselisib, palbociclib, AZD4547) closed for futility; nivolumab plus ipilimumab did not beat nivolumab (S1400I); ramucirumab plus pembrolizumab improved overall survival against standard care (S1800A).

Most of the 22 biomarker-drug cohorts did not meet their pre-set efficacy thresholds; the trial demonstrated national molecular screening and the limits of single-agent matching.

PFS 8.

Continuous cohort reporting: positive signals for pembrolizumab in high tumour mutational burden cancers and trastuzumab plus pertuzumab in ERBB2-amplified colorectal cancer; palbociclib in CDKN2A-altered lung cancer and several other matches were negative.

A milestone in how this cancer is treated.

Classical Hodgkin lymphoma; subsequently HCC, NSCLC, ESCC (second line 2020, first line with chemotherapy 2021), nasopharyngeal

Same

ROS1-positive metastatic NSCLC; NTRK fusion solid tumours (≥12 years, extended to ≥1 month 2023)

Multi-gene companion diagnostic system for NSCLC

Classical Hodgkin lymphoma (first); subsequently urothelial, NSCLC, HCC, ESCC, gastric, nasopharyngeal

Local failure hazard ratio 0.

5-year OS 42.

ALK+ NSCLC after prior ALK TKIs (accelerated)

First-line EGFR-mutant NSCLC (FLAURA)

Unresectable stage III NSCLC after chemoradiation (PACIFIC)

Uncommon EGFR mutations (S768I, L861Q, G719X)

Advanced NSCLC after at least two lines of systemic therapy (ALTER 0303)

ALK-positive NSCLC

First-line metastatic NSCLC with EGFR exon 19 del or L858R

Unresectable stage III NSCLC after chemoradiation

ALK+ NSCLC after prior ALK TKI

First-line EGFR-mutant NSCLC

OS 9.

A milestone in how this cancer is treated.

Full approval (AURA3)

First-line ALK+ NSCLC

ALK-positive metastatic NSCLC after crizotinib

First-line ALK-positive metastatic NSCLC

BRAF V600E metastatic NSCLC

Companion diagnostic for BRAF, ROS1 and EGFR-directed therapies in NSCLC

OS HR 0.

A milestone in how this cancer is treated.

NSCLC after platinum

Squamous NSCLC after platinum

Urothelial carcinoma (later withdrawn); NSCLC

v2: T790M for osimertinib; plasma testing (first liquid biopsy companion diagnostic)

ROS1-positive metastatic NSCLC

EGFR-expressing locally advanced or metastatic squamous NSCLC with gemcitabine and cisplatin

PD-L1 expression to inform atezolizumab treatment in urothelial carcinoma (later NSCLC)

5-year OS 31.

Quality-adjusted life-years 46.

Lean body mass increased (about +1 to +1.

Accelerated approval, EGFR T790M NSCLC after TKI

PD-L1+ NSCLC after platinum

Squamous NSCLC after platinum: first PD-1 in lung cancer

ALK+ NSCLC after crizotinib

Conditional May 2015; full approval 2017

First-line NSCLC with EGFR exon 19 del or L858R

First-line metastatic squamous NSCLC with gemcitabine and cisplatin

CE mark (GBM); pancreatic and NSCLC CE marks 2024-26

EGFR T790M NSCLC

Companion diagnostic for pembrolizumab in NSCLC (TPS)

3-year overall survival 76.

Median overall survival 28.

A milestone in how this cancer is treated.

CheckMate 017/057; pembrolizumab first line for PD-L1 ≥50% follows (KEYNOTE-024, 2016).

ALK-positive metastatic NSCLC after crizotinib

With trametinib: BRAF V600E/K metastatic melanoma; later adjuvant melanoma, BRAF V600E NSCLC, anaplastic thyroid cancer, tumour-agnostic solid tumours and paediatric low-grade glioma

First-line EGFR-mutant NSCLC

Gastric cancer; NSCLC

BRAF V600 melanoma alone or with dabrafenib; later NSCLC and adjuvant melanoma

With dabrafenib: metastatic melanoma; later adjuvant melanoma, NSCLC, anaplastic thyroid cancer, tumour-agnostic BRAF V600E solid tumours, paediatric low-grade glioma

EU brand Giotrif

First-line metastatic NSCLC with EGFR exon 19 del or L858R

EGFR exon 19 deletion / L858R companion diagnostic for erlotinib (v1)

BRAF V600 melanoma; later NSCLC and adjuvant melanoma with trametinib

First-line NSCLC with EGFR exon 19 del or L858R

therascreen EGFR: afatinib in EGFR-mutant NSCLC

ALK-positive metastatic NSCLC

Advanced NSCLC after failure of at least one chemotherapy regimen (ICOGEN)

Lung cancer mortality reduced 20% (NLST) and 24% in men (NELSON).

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

EGFR-mutant NSCLC

Non-squamous NSCLC first line

A milestone in how this cancer is treated.

Soda et al.; crizotinib approved 2011.

NSCLC; later ovarian, cervical, RCC, glioblastoma, HCC

Advanced non-small-cell lung cancer, with vinorelbine and cisplatin

Locally advanced/metastatic NSCLC after chemotherapy

A milestone in how this cancer is treated.

Lynch, Paez, and Pao identify activating EGFR mutations; the birth of lung cancer precision medicine.

NSCLC after chemotherapy (accelerated; restricted 2005)

A milestone in how this cancer is treated.

NSCLC with cisplatin

Palliation of completely or partially obstructing oesophageal cancer; later endobronchial NSCLC and Barrett's high-grade dysplasia

Advanced NSCLC as single agent or with cisplatin

NSCLC, metastatic breast cancer