HER2 (ERBB2) activating mutation — biomarker · CancerIndex

Biomarker · Gene alteration

HER2 (ERBB2) activating mutation

Activating ERBB2 (HER2) mutations, chiefly exon 20 insertions, detected by sequencing of tumor tissue or plasma; used as a predictive marker distinct from HER2 overexpression, notably in non-small cell lung cancer.

CI-BIO-00000004ERBB2 graph →NCIt C96866 Tumor-agnostic · 1 approval row

Also calledHER2 mutation · ERBB2 mutation · HER2 exon 20 insertion · HER2-mutant NSCLC

Tissue-agnostic indications

Approval rows flagged tumor-agnostic (1)

Trastuzumab Deruxtecan US FDA · Dec 20, 2019 · drug in derived setRegulatory approved

The flag is the source's (openFDA label text), never inferred; the full indication text of each row is in the Approvals section below.

Derived

Associated cancers (4)

Cancers mapped in ACCEPTED CIViC predictive, prognostic or diagnostic items whose variant (molecular markers) or gene (gene-level markers) is in this biomarker's scope. Counts by type and native level; each row links to the cancer's evidence tab.

Computedrule biomarker-links-v1

Cancer	Items	Predictive	Prognostic	Diagnostic	Levels A / B / C / D / E
Lung Non-Small Cell Carcinoma	6	6	—	—	4 / 2 / 0 / 0 / 0
Bladder Carcinoma	1	1	—	—	0 / 0 / 1 / 0 / 0
Malignant Breast Neoplasm	1

Derived

Drugs with predictive evidence (7)

Therapies named in in-scope PREDICTIVE CIViC items, plus targets of PREDICTS_RESPONSE_TO knowledge edges from in-scope variants. Sensitivity and resistance are counted separately and never merged into a verdict.

Computedrule biomarker-links-v1

Drug	CIViC items	Sensitivity	Resistance	Best level	Edges (S / R)	Cancer context
Trastuzumab DeruxtecanAdc	3	3	—	A	3 / 0	Lung Non-Small Cell Carcinoma
PertuzumabMonoclonal Antibody	2	2	—	B	1 / 0	Lung Non-Small Cell Carcinoma, Malignant Colorectal Neoplasm
TrastuzumabMonoclonal Antibody	2	2	—	B	1 / 0	Lung Non-Small Cell Carcinoma, Malignant Colorectal Neoplasm
NeratinibSmall Molecule	1	1	—	B	1 / 0	Malignant Breast Neoplasm
Platinum Compound	1	1	—	C	1 / 0	Bladder Carcinoma
SevabertinibSmall Molecule	1	1	—	A	1 / 0	Lung Non-Small Cell Carcinoma
ZongertinibSmall Molecule	1	1	—	A	1 / 0	Lung Non-Small Cell Carcinoma

Curatedcivic items and knowledge edges as curated at the source.

Curated evidence

Predictive evidence items (9)

ACCEPTED CIViC predictive items in scope, grouped by molecular profile and therapy with native level, direction and cancer context. 50 per page.

civicCuratedShowing 1–9 of 9 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
ERBB2 Mutation5
Platinum Compound	Bladder Carcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID1694 In patients with muscle-invasive bladder chancer, a cohort of complete responders to platinum chemotherapy (n=38) and non-responders to platinum chemotherapy (n=33) were evaluated for 178 cancer-assoc… (full text at CIViC) PMID 25636205 · Groenendijk et al., 2016 · Open in CIViC	civic
Trastuzumab Deruxtecan	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID11731 In a phase 2 trial, 152 previously-treated metastatic NSCLC patients harboring mutations in ERBB2 (HER2) were treated with 2 different doses of the HER2 ADC trastuzumab deruxtecan (5.4 mg/kg and 6.4 m… (full text at CIViC) PMID 37694347 · Goto et al., 2023 · Open in CIViC	civic
Pertuzumab + TrastuzumabCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	accepted	EID5980 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Among thirty… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
Zongertinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID12530 The authors report evaluation of zongertinib in a multicohort, phase 1a/1b trial involving patients with advanced or metastatic HER2-mutant non-small cell lung cancer. Three cohorts of patients are re… (full text at CIViC) PMID 40293180 · Heymach et al., 2025 · Open in CIViC	civic
Neratinib	Malignant Breast Neoplasm	Predictive	B	Supports Sensitivity Response	4	accepted	EID5338 16 patients with HER2-mutated metastatic breast cancer were treated with neratinib monotherapy. Of these 16 patients, 14 had known-activating mutations and 2 had mutations of unknown significance. Fiv… (full text at CIViC) PMID 28679771 · Ma et al., 2017 · Open in CIViC	civic
ERBB2 Exon 20 Insertion + ERBB2 Kinase Domain Mutation1
Sevabertinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	2	accepted	EID12808 In an open-label, multicenter, multicohort phase 1–2 study of non-small cell lung carcinoma (NCT05099172; total n = 209), single-agent sevabertinib 20 mg BID demonstrated clinically meaningful activit… (full text at CIViC) PMID 41104928 · Le et al., 2025 · Open in CIViC	civic
ERBB2 Exon 20 Insertion2
Trastuzumab Deruxtecan	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID11765 In a phase 2 trial, 152 metastatic NSCLC patients harboring mutations in ERBB2 (HER2) treated with 2 different doses of the HER2 ADC trastuzumab deruxtecan (5.4 mg/kg and 6.4 mg/kg) resulted in clinic… (full text at CIViC) PMID 37694347 · Goto et al., 2023 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	5	accepted	EID10140 In a phase 2 trial, 91 patients with ERBB2-mutant metastatic non-small-cell lung cancer, refractory to standard treatment, were treated with trastuzumab deruxtecan. The objective response was 55% (95%… (full text at CIViC) PMID 34534430 · Li et al., 2022 · Open in CIViC	civic
ERBB2 Mutation + ERBB3 MutationERBB3 ERBB21
Pertuzumab + TrastuzumabCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID11669 In this clinical study of 38 patients with colorectal cancer (CRC), 10 had CRC with ERBB2/ERBB3 mutation, and were treated with a combination of Pertuzumab and Trastuzumab. A DC of 10% and OR of 0% we… (full text at CIViC) PMID 36315917 · Gupta et al., 2022 · Open in CIViC	civic

Regulatory

Approvals mentioning the linked drugs (100)

Approval records of the derived drug set, plus records whose indication text names this biomarker. Each record names its authority, jurisdiction, indication text and status — a drug approved in one jurisdiction for one indication is not 'approved' in general, and an approval listed here is not necessarily restricted to this biomarker.

Computedrule biomarker-links-v1

openfdaRegulatory50 approval records from 3 sources (hover a row badge for its dataset) · authority, jurisdiction and indication text as published.

Drug	Jurisdiction · authority	Cancer	Indication	Status	Approval date	Source
Trastuzumab Deruxtecan	US FDA	Tumor-agnostic	HER2-Positive Locally Advanced or Metastatic Gastric Cancer as monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen. • HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options* • * These indications are approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ( 14.3 , 14.5 )accelerated	approved	Dec 20, 2019	openfda
Neratinib	CA Health Canada	—	Marketed in Canada as NERLYNX (DIN 02490536) under ATC L01EH02 NERATINIB. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Dec 20, 2019	health-canada-dpd
Neratinib

1 record matched on indication text only (drug not in the derived set). Health Canada DIN rows carry no indication text and only match by drug.

Clinical trials

Active trials (102)

Trials with an active ClinicalTrials.gov status, an intervention mapped to a derived drug and a condition mapped to an associated cancer. 40 recruiting · 18 active phase 3 · 521 in any status. Most recently updated first, 50 per page.

Computedrule biomarker-links-v1

clinicaltrialsPublishedShowing 101–102 of 102 active studies · status and phase as posted by the registrant; each row links to the study record.

NCT	Title	Status	Phase	Enrollment (n)	Sponsor	Countries	Last update	Source
NCT05131893	Neoadjuvant Treatment of Breast Cancer	not yet recruiting	—	300	National Institute of Oncology, HungaryOTHER	1	Nov 23, 2021	clinicaltrials
NCT04973319	Trastuzumab Combined With Pertuzumab for Adjuvant Treatment of Breast Cancer After Neoadjuvant Therapy	not yet recruiting	Phase 3	450	Shengjing HospitalOTHER	1	Jul 22, 2021	clinicaltrials

A study listed here tests a linked drug in a linked cancer; it does not necessarily select participants on this biomarker.

Trastuzumab

EU EMA

—

Breast cancer Metastatic breast cancer Dazublys is indicated for the treatment of adult patients with HER2-positive metastatic breast cancer (MBC): as monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease. Prior chemotherapy must have included at least an anthracycline and a taxane unless patients are unsuitable for these treatments. Hormone receptor-positive patients must also have failed hormonal therapy unless patients are unsuitable for these treatments. in combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease and for whom an anthracycline is not suitable. in combination with docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease. in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor-positive MBC, not previously treated with trastuzumab. Early breast cancer Dazublys is indicated for the treatment of adult patients with HER2-positive early breast cancer. (EBC). following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) (see section 5.1). following adjuvant chemotherapy with doxorubicin and cyclophosphamide in combination with paclitaxel or docetaxel. in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin. in combination with neoadjuvant chemotherapy followed by adjuvant Dazublys therapy for locally advanced (including inflammatory) disease or tumors> 2 cm in diameter (see sections 4.4 and 5.1). Dazublys should only be used in patients with metastatic or early breast cancer whose tumors have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay (see sections 4.4 and 5.1). Metastatic gastric cancer Dazublys in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of adult patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease. Dazublys should only be used in patients with metastatic gastric cancer (MGC) whose tumors have HER2 overexpression as defined by IHC2+ and a confirmatory SISH or FISH result or by an IHC 3+ result. Accurate and validated assay methods should be used (see sections 4.4 and 5.1).

approved

Jun 30, 2025

ema

Trastuzumab

EU EMA

—

Metastatic breast cancer (MBC) For the treatment of adult patients with HER2-positive MBC: as monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease. Prior chemotherapy must have included at least an anthracycline and a taxane unless patients are unsuitable for these treatments. Hormone receptor positive patients must also have failed hormonal therapy unless patients are unsuitable for these treatments. in combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease and for whom an anthracycline is not suitable in combination with docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive MBC, not previously treated with trastuzumab  Early breast cancer (EBC) For the treatment of adult patients with HER2-positive EBC: following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel. in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin. in combination with neoadjuvant chemotherapy followed by adjuvant HD201 therapy, for locally advanced (including inflammatory) disease or tumours >2 cm in diameter.  HD201 should only be used in patients with MBC or EBC whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay. Metastatic gastric cancer (MGC) In combination with capecitabine or 5-fluorouracil and cisplatin for the treatment of adult patients with HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction who have not received prior anti-cancer treatment for their metastatic disease. HD201 should only be used in patients with MGC whose tumours have HER2 overexpression as defined by Immunohistochemistry (IHC) 2+ and a confirmatory silver-enhanced in situ hybridisation (SISH) or fluorescence in situ hybridisation (FISH) result, or by an IHC 3+ result. Accurate and validated assay methods should be used.

approved

Sep 19, 2024

ema

Approval rows flagged tumor-agnostic (1)

Associated cancers (4)

Drugs with predictive evidence (7)

Predictive evidence items (9)

Approvals mentioning the linked drugs (100)

Active trials (102)

Linked publications (8)