Firmonertinib

Summary

Firmonertinib (CHEMBL4297258) is a phase-3 clinical-stage small molecule targeting EGFR; indicated across 4 conditions including non-small cell lung carcinoma and lung adenocarcinoma; with CIViC clinical evidence for 1 variant-indication association (e.g. EGFR Exon 18 Mutation in lung non-small cell carcinoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (EGFR)
• Indications: 4 conditions
• Clinical trials: 49
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 568.6 Da · C28H31F3N8O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4297258
Name	Firmonertinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	118861389
Molecular formula	C28H31F3N8O2
Molecular weight	568.6
InChIKey	GHKOONMJXNWOIW-UHFFFAOYSA-N

SMILES: CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(N=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OCC(F)(F)F

IUPAC name: N-[2-[2-(dimethylamino)ethyl-methylamino]-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]-6-(2,2,2-trifluoroethoxy)-3-pyridinyl]prop-2-enamide

Also known as: AFU, Alflutinib, AST-2818, AST2818, Firmonertinib, Furmonertinib, FIRMONERTINIB

Parent form; salt/anhydrous children: CHEMBL6068476

Patent coverage: 205 distinct patent families (511 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 463 (91%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EGFR	epidermal growth factor receptor	Inhibition		17.5%	P00533

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 1 target gene(s): EGFR.

Top Reactome pathways

37 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	1	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
SHC1 events in ERBB2 signaling	1	EGFR
PLCG1 events in ERBB2 signaling	1	EGFR
PIP3 activates AKT signaling	1	EGFR
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR
GRB2 events in ERBB2 signaling	1	EGFR
PI3K events in ERBB2 signaling	1	EGFR
EGFR interacts with phospholipase C-gamma	1	EGFR
EGFR Transactivation by Gastrin	1	EGFR
Constitutive Signaling by Aberrant PI3K in Cancer	1	EGFR
Signal transduction by L1	1	EGFR
Constitutive Signaling by EGFRvIII	1	EGFR
Inhibition of Signaling by Overexpressed EGFR	1	EGFR
RAF/MAP kinase cascade	1	EGFR
ERBB2 Regulates Cell Motility	1	EGFR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	EGFR
ERBB2 Activates PTK6 Signaling	1	EGFR
Cargo recognition for clathrin-mediated endocytosis	1	EGFR
Clathrin-mediated endocytosis	1	EGFR
PTK6 promotes HIF1A stabilization	1	EGFR
Downregulation of ERBB2 signaling	1	EGFR
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	EGFR
Extra-nuclear estrogen signaling	1	EGFR
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	EGFR

Dominant GO biological processes

GO term	Targets
cell morphogenesis	1
ossification	1
embryonic placenta development	1
positive regulation of protein phosphorylation	1
hair follicle development	1
ubiquitin-dependent protein catabolic process	1
signal transduction	1
cell surface receptor signaling pathway	1
epidermal growth factor receptor signaling pathway	1
salivary gland morphogenesis	1
learning or memory	1
positive regulation of cell population proliferation	1
gene expression	1
protein ubiquitination	1
cerebral cortex cell migration	1

Indications & clinical

Indications

4 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
lung adenocarcinoma	2	MONDO:0005061	EFO:0000571
lung neoplasm	2	MONDO:0021117	MONDO:0008903
neoplasm	2	MONDO:0005070	EFO:0000616

Clinical trials

Total trials: 49.

Phase distribution

Phase	Trials
PHASE2	30
Not specified	6
PHASE1	5
PHASE3	4
PHASE1/PHASE2	3
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07092202	PHASE4	RECRUITING	Firmonertinib Combined With Intrathecal Injection for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases
NCT06674343	PHASE3	RECRUITING	Furmonertinib 160mg as First-line Treatment in Locally Advanced or Metastatic NSCLC With EGFR Classical Mutations
NCT06956001	PHASE3	RECRUITING	Firmonertinib Versus Platinum Based Chemotherapy as First-line Treatment for NSCLC With EGFR PACC or EGFR l861q Mutation
NCT07010419	PHASE3	RECRUITING	A Study to Assess the Efficacy and Safety of Firmonertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB - IIIB NSCLC With Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations, Following Complete Surgical Resection With or Without Adjuvant Chemotherapy（FIRMOST）
NCT07185997	PHASE3	RECRUITING	Study to Evaluate Efficacy and Safety of Firmonertinib Compared With Investigator’s Choice of EGFR Inhibitor as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic NSCLC With EGFR P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations
NCT05334277	PHASE2	RECRUITING	Furmonertinib Monotherapy and Combination Therapy in Advanced EGFR Mutant NSCLC With Uncleared ctDNA
NCT05379803	PHASE2	RECRUITING	High-dose Furmonertinib for First-line Treatment of EGFR Mutated NSCLC With Central Nervous System (CNS) Metastases
NCT05445310	PHASE2	RECRUITING	Adjuvant Furmonertinib in Stage IA With High Risk Factors and Stage IB Non-small Cell Lung Cancer
NCT05466149	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Furmonertinib in Patients With Locally Advanced or Metastatic NSCLC With EGFR Exon 20 Insertion
NCT05503667	PHASE2	RECRUITING	Neoadjuvant Furmonertinib Plus Bevacizumab or Furmonertinib Monotherapy for Resectable and Potentially Resectable Stage III-IVA EGFR Mutation-Positive Lung Adenocarcinoma
NCT05994131	PHASE1/PHASE2	RECRUITING	IN10018 Combination Therapy in Advanced EGFR Mutation-positive NSCLC
NCT06185400	PHASE2	NOT_YET_RECRUITING	RC48 Combined With EGFR or HER2 TKI for Locally Advanced or Metastatic NSCLC Patients With HER2 Alterations
NCT06192849	PHASE2	RECRUITING	To Assess the Efficacy and Safety of Furmonertinib in Patients With Epidermal Growth Factor Receptor 20ins Mutation Positive Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy
NCT06319950	PHASE2	NOT_YET_RECRUITING	High-dose Furmonertinib Versus Osimertinib in Advanced EGFRm NSCLC Patients With Brain Metastases
NCT06394674	PHASE2	RECRUITING	High-dose Furmonertinib in the Treatment in Patients With Advanced, Metastatic NSCLC With Progressed After First- or Second-line Treatment With Osimertinib
NCT06483672	PHASE2	NOT_YET_RECRUITING	Furmonertinib Combined With Anlotinib in Lung Adenocarcinoma Patients With EGFR Mutations and Brain Metastases
NCT07182708	PHASE2	NOT_YET_RECRUITING	High-Dose Firmonertinib Plus Bevacizumab as Neoadjuvant Therapy for Resectable EGFRm Stage II-IIIB NSCLC
NCT07193160	PHASE2	NOT_YET_RECRUITING	Sacituzumab Tirumotecan in Combination With Furmonertinib as Second-line Treatment for EGFR-mutant Advanced or Metastatic NSCLC After Failure of First-line Third-generation EGFR-TKI Therapy
NCT07229599	PHASE1/PHASE2	RECRUITING	A Study of MHB036C Combined With Anti-tumor Therapies in Patients With Advanced Lung Cancer
NCT07298148	PHASE2	NOT_YET_RECRUITING	Firmonertinib 160 mg in Patients With EGFR-Mutant Advanced NSCLC Demonstrating SD After 8 Week Induction With Firmonertinib 80 mg
NCT07304739	PHASE2	RECRUITING	Furmonertinib Combined With Intrathecal Chemotherapy and Stereotactic Radiotherapy (SRT) for EGFR-Mutated NSCLC Patients With Brain Parenchymal and Leptomeningeal Metastases
NCT07314216	PHASE2	NOT_YET_RECRUITING	Firmonertinib Combined With Definitive Radiotherapy in Stage III Unresectable EGFR Uncommon Mutant Pulmonary Adenocarcinoma
NCT07365410	PHASE2	NOT_YET_RECRUITING	Furmonertinib 160mg vs 80mg + Chemotherapy in EGFR-Mutated NSCLC With Brain Metastases: Efficacy and Safety Study
NCT07482605	PHASE2	NOT_YET_RECRUITING	Furmonertinib Plus Radiotherapy for EGFR+ NSCLC With Pleural Effusion
NCT07517640	PHASE2	NOT_YET_RECRUITING	Combining Furmonertinib With Local Therapy for Inoperable Early-stage Lung Cancer: A Phase II Trial
NCT03452592	PHASE2	TERMINATED	Efficacy and Safety of Alflutinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer Patients With T790M
NCT04895930	PHASE2	UNKNOWN	Furmonertinib Combined With Anlotinib as the First-line Treatment in Patients With EGFR Mutation-positive NSCLC
NCT04965831	PHASE2	UNKNOWN	Furmonertinib as Perioperation Therapy in Stage IIIA-IIIB (N1-N2) Resectable EGFR Mutated Lung Adenocarcinoma (FRONT)
NCT04970693	PHASE2	UNKNOWN	A Study of Furmonertinib Combined With Radiotherapy for Non-small Cell Lung Cancer With Oligoprogression
NCT04982900	PHASE2	UNKNOWN	Treatment of EGFR-TKI for Residual Lesions of Multiple Synchronous Ground-glass Opacities
NCT05079022	PHASE1/PHASE2	UNKNOWN	ctDNA-MRD Based Adjuvant Targeted Therapy for EGFR Positive Stage I Lung Adenocarcinomas
NCT05165355	PHASE2	UNKNOWN	Adjuvant Targeted-therapy for Patients With Resected High-risk EGFR-mutant Stage IB-IIA Non-small Cell Lung Carcinoma
NCT05255406	PHASE2	UNKNOWN	Efficacy and Safety of Furmonertinib in EGFR-Mutant, PD-L1+ Patients With Locally Advanced or Metastatic NSCLC (FUTURE)
NCT05465343	PHASE2	COMPLETED	Furmonertinib in EGFR-Mutant NSCLC With Brain Metastases (iFORCE)
NCT05548348	PHASE2	UNKNOWN	First-line Furmonertinib in Advanced NSCLC Patients With EGFR Uncommon Mutation
NCT05987826	PHASE2	UNKNOWN	Study of Furmonertinib as Neoadjuvant Therapy for Resectable Stage Ⅱ-ⅢB EGFR Sensitive Mutant NSCLC
NCT06339242	PHASE2	UNKNOWN	A Study of Furmonertinib Combined With Chemotherapy in the Treatment of NSCLC With Leptomeningeal Metastasis
NCT06812871	PHASE2	COMPLETED	High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis
NCT04858958	PHASE1	ACTIVE_NOT_RECRUITING	Study of FURMONERTINIB in Patients With NSCLC Having Exon 20 Insertion Mutation
NCT05364073	PHASE1	ACTIVE_NOT_RECRUITING	Study of Furmonertinib in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Activating, Including Uncommon, Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Mutations

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
EGFR Exon 18 Mutation	Lung Non-small Cell Carcinoma	Sensitivity/Response	Firmonertinib	CIViC D	EID12781

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

158 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR
ALECTINIB	ChEMBL	Phase 4 (approved)	EGFR
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR
BACITRACIN	ChEMBL	Phase 4 (approved)	EGFR
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR
CERITINIB	ChEMBL	Phase 4 (approved)	EGFR
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR
CHROMIC CHLORIDE	ChEMBL	Phase 4 (approved)	EGFR
CISPLATIN	ChEMBL	Phase 4 (approved)	EGFR
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR
CRIZOTINIB	ChEMBL	Phase 4 (approved)	EGFR
DACOMITINIB	ChEMBL	Phase 4 (approved)	EGFR
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR
DOBUTAMINE	ChEMBL	Phase 4 (approved)	EGFR
DOCETAXEL	ChEMBL	Phase 4 (approved)	EGFR
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR
GEFITINIB	ChEMBL	Phase 4 (approved)	EGFR
GENTIAN VIOLET	ChEMBL	Phase 4 (approved)	EGFR
GILTERITINIB	ChEMBL	Phase 4 (approved)	EGFR
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB DITOSYLATE	ChEMBL	Phase 4 (approved)	EGFR
LAZERTINIB	ChEMBL	Phase 4 (approved)	EGFR
LEVODOPA	ChEMBL	Phase 4 (approved)	EGFR
LORLATINIB	ChEMBL	Phase 4 (approved)	EGFR
METHYLDOPA	ChEMBL	Phase 4 (approved)	EGFR
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR
MOBOCERTINIB	ChEMBL	Phase 4 (approved)	EGFR
MONTELUKAST	ChEMBL	Phase 4 (approved)	EGFR
NELFINAVIR	ChEMBL	Phase 4 (approved)	EGFR
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	EGFR
OLMUTINIB	ChEMBL	Phase 4 (approved)	EGFR
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR
PERHEXILINE	ChEMBL	Phase 4 (approved)	EGFR
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR
SULOCTIDIL	ChEMBL	Phase 4 (approved)	EGFR
SUNITINIB	ChEMBL	Phase 4 (approved)	EGFR
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR
TERFENADINE	ChEMBL	Phase 4 (approved)	EGFR
THIORIDAZINE	ChEMBL	Phase 4 (approved)	EGFR
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR