HER2 (ERBB2) overexpression / amplification

HER2 protein overexpression or ERBB2 gene amplification measured on tumor tissue; used as a predictive marker for HER2-directed therapy in breast, gastric/gastro-esophageal and other carcinomas.

CI-BIO-00000001ERBB2 graph →NCIt C68748 Tumor-agnostic · 2 approval rows

Also calledHER2 · HER2/neu · ERBB2 · HER2-positive · HER2 amplification · HER2-low

Tissue-agnostic indications

Approval rows flagged tumor-agnostic (2)

Trastuzumab Deruxtecan US FDA · Dec 20, 2019 · matched on indication textRegulatory approved
Trastuzumab Deruxtecan US FDA · Dec 20, 2019 · drug + indication textRegulatory 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 (22)

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
HER2-Positive Breast Carcinoma	28	28	—	—	2 / 21 / 0 / 5 / 0
Malignant Colorectal Neoplasm	10	10	—	—	0 / 9 / 0 / 1 / 0
Malignant Breast Neoplasm	5

Derived

Drugs with predictive evidence (27)

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
TrastuzumabMonoclonal Antibody	38	38	—	A	31 / 0	Bladder Carcinoma, Cholangiocarcinoma, Endometrial Serous Adenocarcinoma, Gastric Adenocarcinoma +12
LapatinibSmall Molecule	11	11	—	B	10 / 0	Childhood Ependymoma, Gastric Adenocarcinoma, Head and Neck Squamous Cell Carcinoma, HER2-Positive Breast Carcinoma +2
PertuzumabMonoclonal Antibody	11	11	—	B	10 / 0	Bladder Carcinoma, Cholangiocarcinoma, HER2-Positive Breast Carcinoma, Malignant Biliary Tract Neoplasm +4
AfatinibSmall Molecule	8	8	—	B	7 / 0	HER2-Positive Breast Carcinoma, Malignant Colorectal Neoplasm, Pancreatic Adenocarcinoma
Trastuzumab EmtansineAdc	6	6	—	B	6 / 0	HER2-Positive Breast Carcinoma, Lung Non-Small Cell Carcinoma
CetuximabMonoclonal Antibody	5	—	5	B	0 / 4	Malignant Colorectal Neoplasm
CapecitabineSmall Molecule	5	4	1	B	3 / 0	HER2-Positive Breast Carcinoma, Malignant Colorectal Neoplasm, Malignant Pancreatic Neoplasm, Malignant Salivary Gland Neoplasm
DocetaxelSmall Molecule	2	2	—	B	2 / 0	HER2-Positive Breast Carcinoma
NeratinibSmall Molecule	2	2	—	A	2 / 0	HER2-Positive Breast Carcinoma
PictilisibSmall Molecule	2	2	—	D	2 / 0	HER2-Positive Breast Carcinoma, Malignant Breast Neoplasm
Trastuzumab DeruxtecanAdc	2	2	—	A	2 / 0	Malignant Gastric Neoplasm, Solid Neoplasm
A66	1	1	—	D	1 / 0	HER2-Positive Breast Carcinoma
AKTi-1/2	1	1	—	D	1 / 0	Malignant Breast Neoplasm
ErlotinibSmall Molecule	1	—	1	C	0 / 1	Lung Adenocarcinoma
GefitinibSmall Molecule	1	—	1	C	0 / 1	Lung Adenocarcinoma
IrinotecanSmall Molecule	1	1	—	C	1 / 0	Lung Small Cell Carcinoma
MargetuximabMonoclonal Antibody	1	1	—	A	1 / 0	Malignant Breast Neoplasm
MTOR Kinase Inhibitor PP242	1	1	—	D	1 / 0	Malignant Breast Neoplasm
PaclitaxelSmall Molecule	1	1	—	C	1 / 0	Malignant Salivary Gland Neoplasm
PalbociclibSmall Molecule	1	1	—	D	1 / 0	HER2-Positive Breast Carcinoma
PanitumumabMonoclonal Antibody	1	—	1	B	0 / 1	Malignant Colorectal Neoplasm
PilaralisibSmall Molecule	1	1	—	D	1 / 0	HER2-Positive Breast Carcinoma
Zoledronic AcidSmall Molecule	1	1	—	C	1 / 0	Malignant Salivary Gland Neoplasm
DacomitinibSmall Molecule	1	1	—	B	—	Lung Non-Small Cell Carcinoma
GemcitabineSmall Molecule	1	1	—	B	—	Malignant Pancreatic Neoplasm
OxaliplatinSmall Molecule	1	—	1	B	—	Malignant Colorectal Neoplasm
Tgx 221	1	1	—	D	—	HER2-Positive Breast Carcinoma

Curatedcivic items and knowledge edges as curated at the source.

Curated evidence

Predictive evidence items (71)

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

civicCuratedShowing 1–50 of 71 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 Amplification48
Pertuzumab + TrastuzumabCombination	Bladder Carcinoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID5982 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. Three of nin… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
Lapatinib	Childhood Ependymoma	Predictive	B	Supports Sensitivity Response	1	accepted	EID9778 From a phase one clinical trial, pediatric patients with refractory CNS malignancies were administered 300-1150 mg/m2 twice daily of ERBB2 and EGFR inhibitor lapatinib. The maximum-tolerated dose was … (full text at CIViC) PMID 20713864 · Fouladi et al., 2010 · Open in CIViC	civic
Pertuzumab + TrastuzumabCombination	Cholangiocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID7638 A patient with cholangiocarcinoma harboring with ERBB2 amplification (3+) detected by circulating tumor DNA testing and confirmed by tissue-based testing was treated with trastuzumab and pertuzumab. T… (full text at CIViC) PMID 31453370 · Yarlagadda et al., 2019 · Open in CIViC	civic
Trastuzumab	Endometrial Serous Adenocarcinoma	Predictive	C	Supports Sensitivity Response	4	accepted	EID1097 HER2 expression in uterine serous papillary carcinoma (USPC) is thought to be associated with poor prognosis and may act as a targetable driver mutation in this cancer. HER2 overexpression in USPC is… (full text at CIViC) PMID 18555254 · Santin et al., 2008 · Open in CIViC	civic
Lapatinib	Gastric Adenocarcinoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID1023 TyTAN, a Phase III study in Asian patients, looked at addition of tyrosine kinase inhibitor lapatinib to chemptherapy in advanced HER2 positive gastric cancer. Primary endpoint was Overall Survival (… (full text at CIViC) PMID 24868024 · Satoh et al., 2014 · Open in CIViC	civic
Trastuzumab	Gastric Adenocarcinoma	Predictive	A	Supports Sensitivity Response	4	accepted	EID1499 ToGA, a Phase III study (NCT01041404) addressed use of trastuzumab in HER2 positive (overexpression or amplification) advanced gastric cancer, where chemotherapy using fluoropyrimidine-based and plati… (full text at CIViC) PMID 20728210 · Bang et al., 2010 · Open in CIViC	civic
〃	Gastric Adenocarcinoma	Predictive	B	Supports Sensitivity Response	4	accepted	EID1022 ToGA, a Phase III study (NCT01041404) addressed use of trastuzumab in HER2 positive advanced gastric cancer, where chemotherapy using fluoropyrimidine-based and platinum-based combinations had been co… (full text at CIViC) PMID 20728210 · Bang et al., 2010 · Open in CIViC	civic
A66	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1381 Pharmacologic (A66; p110alpha specific inhibitor) or genetic (cre-mediated knockout) ablation of the p110alpha PI3K isoform reduced tumor growth and tumor formation, respectively, in athymic mice tran… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC	civic
Afatinib	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID961 A phase II study involving adult female patients, >=18 years, with stage IIIB or IV HER2-positive (by IHC and/or in situ fluorescence) metastatic breast cancer. All patients were previously treated wi… (full text at CIViC) PMID 22418700 · Lin et al., 2012 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID1011 This Phase II trial (LUX-Breast 3 - NCT01441596) compared afatinib, afatinib plus vinorelbine, or investigator's choice of treatment. 121 patients with HER2 overexpressing breast cancer with CNS recu… (full text at CIViC) PMID 26596672 · Cortés et al., 2015 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID1012 LUX-Breast 1 is a phase 3 trial (NCT01125566) which enrolled 508 patients with metastatic HER2 positive BC who had progressed after adjuvant or first-line trastuzumab. It was thought that the wider ra… (full text at CIViC) PMID 26822398 · Harbeck et al., 2016 · Open in CIViC	civic
Afatinib + Lapatinib + TrastuzumabSubstitutes	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	2	accepted	EID887 In this phase 2 trial, treatment-naive, ERBB2-positive (by IHC) breast cancer patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to afatinib (n = 10), lapatinib (n = 8), or t… (full text at CIViC) PMID 25537159 · Rimawi et al., 2015 · Open in CIViC	civic
Afatinib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID1013 Trastuzumab resistance is thought to consist of multiple compensatory mechanisms involving ErbB family members such as increased signaling through ErbB family heterodimers. The irreversible TKI afati… (full text at CIViC) PMID 25370464 · Ring et al., 2015 · Open in CIViC	civic
Capecitabine + LapatinibCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1132 This Phase III trial took patients with locally advanced or metastatic HER2 (ERBB2) positive breast cancer that had progressed on prior trastuzumab treatment. Patients were given capecitabine (n=161)… (full text at CIViC) PMID 17192538 · Geyer et al., 2006 · Open in CIViC	civic
Lapatinib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1007 In light of results showing increased PFS using mAB plus TKI in heavily pretreated patients, the efficacy of trastuzumab plus lapatinib in a neoadjuvant setting with untreated stage II or IIIA HER2 po… (full text at CIViC) PMID 22493419 · Guarneri et al., 2012 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1009 This Phase III study (EGF104900) was motivated by preclinical and other data demonstrating synergistic activity between lapatinib and trastuzumab against HER2 positive breast cancer (BC) cells. In th… (full text at CIViC) PMID 20124187 · Blackwell et al., 2010 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1439 In a randomized open label phase 3 study (NCT00553358), women with HER2 positive primary breast cancer treated with lapatinib plus trasuzumab had higher rates of pathological complete responses than s… (full text at CIViC) PMID 22257673 · Baselga et al., 2012 · Open in CIViC	civic
Neratinib	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID761 Oral neratinib showed objective response rates of 24 and 56% respectively in prior-trastuzumab (n=63) and trastuzumab-naive (n=64) cohorts in a Phase II trial. As for the primary endpoint, the 16-week… (full text at CIViC) PMID 20142587 · Burstein et al., 2010 · Open in CIViC	civic
Neratinib + TrastuzumabSequential	HER2-Positive Breast CarcinomaALIAS	Predictive	A	Supports Sensitivity Response	4	accepted	EID1113 In this two arm, Phase III study (NCT00878709) of the efficacy of a 12 month course of the TKI neratinib after trastuzumab-based adjuvant therapy of early stage HER2-positive breast cancer was assesse… (full text at CIViC) PMID 26874901 · Chan et al., 2016 · Open in CIViC	civic
Docetaxel + Pertuzumab + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	5	accepted	EID1077 CLEOPATRA (NCT00567190) was a Phase III, randomized and double-blind, placebo-controlled study of 808 patients with HER2-positive metastatic breast cancer. Patients were HER2-positive by IHC3+ or FIS… (full text at CIViC) PMID 25693012 · Swain et al., 2015 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1437 In a randomized phase 3 trial, HER2 positive metastatic breast cancer patients given first-line treatment of pertuzumab plus trastuzumb plus docetaxel experienced improved progression free survival (1… (full text at CIViC) PMID 22149875 · Baselga et al., 2012 · Open in CIViC	civic
Pictilisib	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	3	accepted	EID1380 The HER2/Neu mammary tumor mouse model MMTV-NeuT was employed to demonstrate dependence of HER2 tumor formation on PIK3 p110alpha isoform. MMTV-NeuT mice were crossed with floxed p110alpha mice. Diass… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC	civic
Tgx 221	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Does Not Support Sensitivity Response	3	accepted	EID1382 Treatment of cells obtained from MMTV-NeuT mouse mammary tumors with the p110beta selective inhibitor TGX-221 showed significant but minimal reductions in lipid kinase activity and negligible reductio… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC	civic
Trastuzumab	HER2-Positive Breast CarcinomaALIAS	Predictive	A	Supports Sensitivity Response	4	accepted	EID1122 HERA was a Phase III trial assessing application of trastuzumab in an extended adjuvant setting. Patients were HER2 positive with completely excised invasive BC, node positive or negative, and having… (full text at CIViC) PMID 16236737 · Piccart-Gebhart et al., 2005 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	5	accepted	EID528 A randomized clinical trial of 469 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved time to disease progression, objective response rate, and duration … (full text at CIViC) PMID 11248153 · Slamon et al., 2001 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	5	accepted	EID529 A randomized clinical trial of 186 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved overall survival, response rate, response duration, time to progres… (full text at CIViC) PMID 15911866 · Marty et al., 2005 · Open in CIViC	civic
Capecitabine + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1133 In this Phase III trial, trastuzumab-based treatment was assessed in women with locally advanced or metastatic HER2 positive breast cancer who had progressed on trastuzumab. Patients had 12 weeks or … (full text at CIViC) PMID 19289619 · von Minckwitz et al., 2009 · Open in CIViC	civic
Trastuzumab Emtansine	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1159 The Phase III trial, TH3RESA (NCT01419197), was performed in patients with advanced HER2 breast cancer that was heavily pretreated. Patients were required to have prior exposure to trastuzumab and la… (full text at CIViC) PMID 24793816 · Krop et al., 2014 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1160 The EMILIA study (NCT00829166) was a Phase II trial to assess the efficacy of trastuzumab emtansine (T-DM1, n=495) in comparison to lapatinib plus capecitabine (n=496), in treatment of advanced HER2 p… (full text at CIViC) PMID 23020162 · Verma et al., 2012 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID1432 In a randomized phase II study, first line treatment of HER2-positive metastatic breast cancer with trastuzumab emtansine (T-DM1) resulted in improved progression free survival and fewer serious adver… (full text at CIViC) PMID 23382472 · Hurvitz et al., 2013 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1764 In the single arm Phase II study (TDM4258g) breast cancer patients who had progressed on previous anti-HER2 therapy were given transtuzumab emtansine (T-DM1), a HER2 monoclonal antibody and antimicrot… (full text at CIViC) PMID 21172893 · Burris et al., 2011 · Open in CIViC	civic
Lapatinib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID1008 This Phase III trial compared the activity of lapatinib vs. trastuzumab vs. sequential trastuzumab followed by lapatinib vs. lapatinib plus trastuzumab in an adjuvant treatment setting. 8381 women we… (full text at CIViC) PMID 26255196 · Zardavas et al., 2015 · Open in CIViC	civic
Palbociclib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1561 In a panel of 47 breast cancer cell lines, HER2 overexpressing cells were among those more sensitive to CDK4/6 inhibitor Palbociclib (PD0332991). In the trastuzumab sensitive cell line Bt474, palbocic… (full text at CIViC) PMID 19874578 · Finn et al., 2009 · Open in CIViC	civic
Pilaralisib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	4	accepted	EID1448 In 5 trastuzumab resistant HER2 overexpressing breast cancer cell lines, combination of the pan-PI3K inhibitor XL147 (pilaralisib) and trastuzumab treatment induced cell death to similar or greater le… (full text at CIViC) PMID 23204226 · Chakrabarty et al., 2013 · Open in CIViC	civic
Erlotinib + GefitinibSubstitutes	Lung Adenocarcinoma	Predictive	C	Supports Resistance	1	accepted	EID1393 155 patients with lung adenocarcinomas underwent rebiopsy and genotyping (EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS, PIK3CA and FISH for MET and HER2) after the development of acquired resistance to E… (full text at CIViC) PMID 23470965 · Yu et al., 2013 · Open in CIViC	civic
Dacomitinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID1891 Phase 2 trial of ERBB-inhibitor dacomitinib in stage IIIB/IV lung cancers with HER2 mutations or amplification. 4 patients with HER2 amplified NSCLC were enrolled in the trial, no one among them had a… (full text at CIViC) PMID 25899785 · Kris et al., 2015 · Open in CIViC	civic
Trastuzumab	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID1041 In this phase II trial with 2 arms, 103 patients with untreated stage IIIB/IV HER2 positive NSCLC were given gemcitabine-cisplatin with or without trastuzumab. HER2 positivity was broadly defined as … (full text at CIViC) PMID 14679114 · Gatzemeier et al., 2004 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID1042 In this phase II trial a small group of patients with IHC2+ or IHC3+ HER2 NSCLC, in which primary platinum-based therapy had failed, were given either docetaxel or trastuzumab after which both groups … (full text at CIViC) PMID 14967075 · Lara et al., 2004 · Open in CIViC	civic
Trastuzumab Emtansine	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	accepted	EID1050 Efficacy of trastuzumab in HER2 overexpressing NSCLC remains unclear. In this study using a panel of NSCLC HER2 overexpressing cell lines, antiproliferative effects of trastuzumab emtansine (T-DM1) w… (full text at CIViC) PMID 24898067 · Cretella et al., 2014 · Open in CIViC	civic
Irinotecan + TrastuzumabCombination	Lung Small Cell Carcinoma	Predictive	C	Supports Sensitivity Response	4	accepted	EID1044 This report details 2 case studies in relapsed HER2 positive SCLC. In the first case, a 50 pack-year patient showed intense non-mutant HER2 expression by IHC without DNA amplification, and had underg… (full text at CIViC) PMID 25601188 · Kinehara et al., 2015 · Open in CIViC	civic
Pertuzumab + TrastuzumabCombination	Malignant Biliary Tract NeoplasmALIAS	Predictive	B	Supports Sensitivity Response	2	accepted	EID5983 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. Two of seven… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
AKTi-1/2	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	3	accepted	EID760 Xenografts established from breast cancer cell lines with ERBB2 amplification and PIK3CA mutation (BT474) or PIK3CA mutation alone (MCF7) were effectively inhibited in-vivo with an AKT1/2-inhibitor (A… (full text at CIViC) PMID 18725974 · She et al., 2008 · Open in CIViC	civic
Lapatinib + TrastuzumabCombination	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	3	accepted	EID1006 In-vitro studies using ERBB2 over-expressing breast cancer cell lines BT474 and SKBR3 (with ERBB2 amplification) showed apoptosis under either labatinib or trastuzumab treatment. A marked synergistic… (full text at CIViC) PMID 16091755 · Xia et al., 2005 · Open in CIViC	civic
Margetuximab	Malignant Breast Neoplasm	Predictive	A	Supports Sensitivity Response	5	accepted	EID11249 In this phase III, randomized, open-label trial, 536 patients with HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, with at least one being for metastatic disease. T… (full text at CIViC) PMID 33480963 · Rugo et al., 2021 · Open in CIViC	civic
MTOR Kinase Inhibitor PP242	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	2	accepted	EID1613 In a panel of 31 breast cancer cell lines with varied mutation backgrounds, 10 cell lines harbored HER2 (ERBB2) amplification. Sensitivity to the mTORC1/2 inhibitor PP242 was assessed, and 8/10 HER2 p… (full text at CIViC) PMID 21358673 · Weigelt et al., 2011 · Open in CIViC	civic
Pictilisib	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	3	accepted	EID2071 This preclinical study tested the efficacy of GDC-0941, a selective inhibitor of class I PI3K, on several cell lines of breast cancer. Sensitivity and resistance was categorized as less than and more … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
Afatinib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID7807 Afatinib monotherapy was tested in patient-derived colorectal cancer (M051) mouse xenografts and gastric cancer cell-line (NCI-N87) mouse xenografts. Tumor shrinkage was observed and tumor volume was… (full text at CIViC) PMID 26296355 · Leto et al., 2015 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	4	accepted	EID1686 A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC) PMID 22586653 · Bertotti et al., 2011 · Open in CIViC	civic
ERBB2 Overexpression2
Lapatinib	Head and Neck Squamous Cell Carcinoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID1992 Case report of a 60-year old patient with p16 positive tumor of the tonsil with lung metastases after primary radiochemotherapy. The metastases were analyzed using a commercial molecular analysis and … (full text at CIViC) PMID 28061634 · Seim et al., 2017 · Open in CIViC	civic
Trastuzumab Emtansine	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID4840 Trastuzumab emtansine has its indication for patients with HER2-positive metastatic breast cancer after therapy with Trastuzumab and Taxane, approval based on PFS and preliminary OS data. EMILIA was a… (full text at CIViC) PMID 28526536 · Diéras et al., 2017 · Open in CIViC	civic

Regulatory

Approvals mentioning the linked drugs (500)

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
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 )

9 records 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 (957)

Trials with an active ClinicalTrials.gov status, an intervention mapped to a derived drug and a condition mapped to an associated cancer. 456 recruiting · 250 active phase 3 · 4,931 in any status. Most recently updated first, 50 per page.

Computedrule biomarker-links-v1

clinicaltrialsPublishedShowing 1–50 of 957 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
NCT04793958	Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)	active not recruiting	Phase 3	461	Mirati Therapeutics Inc.INDUSTRY	32	Sep 28, 2026	clinicaltrials
NCT05256225	Testing the Addition of Herceptin Hylecta or Phesgo to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma	recruiting	Phase 3	360	National Cancer Institute (NCI)NIH	3	Sep 28, 2026	clinicaltrials
NCT05482893	Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or Targeted Therapy and/or ICI, for the Treatment of Patients With Advanced Gastrointestinal Cancers, Including Gastric, Gastroesophageal Junction, Pancreatic Ductal or Biliary Tract Carcinomas (the TWINPEAK Study)	recruiting	Phase 1 / Phase 2	350	Phanes TherapeuticsINDUSTRY	1	Sep 28, 2026	clinicaltrials
NCT05867251	Study of AVZO-021 in Patients With Advanced Solid Tumors	recruiting	Phase 1 / Phase 2	430	Avenzo Therapeutics, Inc.INDUSTRY	2	Sep 28, 2026	clinicaltrials
NCT06586957	A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors	recruiting	Phase 1	238	NiKang Therapeutics, Inc.INDUSTRY	1	Sep 28, 2026	clinicaltrials
NCT06623422	A Study of Pembrolizumab (MK-3475) With or Without Intismeran Autogene (V940) in Participants With Non-small Cell Lung Cancer (V940-009/INTerpath-009)	recruiting	Phase 3	680	Merck Sharp & Dohme LLCINDUSTRY	31	Sep 28, 2026	clinicaltrials
NCT06787339	Capecitabine in Low Risk Triple Negative Breast Cancer(Calorite)	recruiting	Phase 2	198	Fudan UniversityOTHER	1	Sep 28, 2026	clinicaltrials
NCT06820463	A Study to Evaluate the Adverse Events, and Efficacy of Intravenous (IV) of Telisotuzumab Adizutecan in Combination With IV Oxaliplatin, Fluorouracil, Folinic Acid/Leucovorin, Bevacizumab, Panitumumab in Adult Participants With Metastatic Colorectal Cancer(AndroMETa-CRC)	recruiting	Phase 2	390	AbbVieINDUSTRY	15	Sep 28, 2026	clinicaltrials
NCT07152782	T-DXd With or Without Neratinib for HER2 Positive Breast Cancer With Brain Metastasis(THUNDER)	recruiting	Phase 2	202	Fudan UniversityOTHER	1	Sep 28, 2026	clinicaltrials
NCT07621718	Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )(RASolute 305)	recruiting	Phase 3	670	Revolution Medicines, Inc.INDUSTRY	2	Sep 28, 2026	clinicaltrials
NCT02595931	M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery	active not recruiting	Phase 1	66	National Cancer Institute (NCI)NIH	1	Sep 25, 2026	clinicaltrials
NCT04253964	Pilot Study of Performance Status 2 vs. Performance Status 0-1 Non-small Cell Lung Cancer Patients Treated With Chemo/Immunotherapy	recruiting	Phase 2	105	Wake Forest University Health SciencesOTHER	1	Sep 25, 2026	clinicaltrials
NCT04267848	Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-small Cell Lung Cancer, an ALCHEMIST Treatment Trial (Chemo-IO [ACCIO])	recruiting	Phase 3	1,210	National Cancer Institute (NCI)NIH	2	Sep 25, 2026	clinicaltrials
NCT05132075	Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer(KontRASt-02)	active not recruiting	Phase 3	95	Novartis PharmaceuticalsINDUSTRY	25	Sep 25, 2026	clinicaltrials
NCT06103864	A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast05)	recruiting	Phase 3	625	AstraZenecaINDUSTRY	24	Sep 25, 2026	clinicaltrials
NCT06203600	Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial	recruiting	Phase 2 / Phase 3	224	National Cancer Institute (NCI)NIH	1	Sep 25, 2026	clinicaltrials
NCT06312137	A Study to Assess Efficacy and Safety of Pembrolizumab With or Without Sacituzumab Tirumotecan (MK- 2870) in Adult Participants With Resectable Non Small Cell Lung Cancer (NSCLC) Not Achieving Pathological Complete Response (pCR) (MK-2870-019)(TroFuse-019)	recruiting	Phase 3	780	Merck Sharp & Dohme LLCINDUSTRY	31	Sep 25, 2026	clinicaltrials
NCT06369259	Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer	recruiting	Phase 2	33	M.D. Anderson Cancer CenterOTHER	1	Sep 25, 2026	clinicaltrials
NCT06377852	The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study	recruiting	Phase 3	500	American Society of Clinical OncologyOTHER	1	Sep 25, 2026	clinicaltrials
NCT06385080	A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer(OrigAMI-4)	recruiting	Phase 1 / Phase 2	287	Janssen Research & Development, LLCINDUSTRY	11	Sep 25, 2026	clinicaltrials
NCT07007559	ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer(ASPEN-09-03)	recruiting	Phase 2	120	ALX Oncology Inc.INDUSTRY	8	Sep 25, 2026	clinicaltrials
NCT07219212	A Study of JNJ-90301900 in Combination With Chemoradiation Therapy in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma(LUMIRAY)	recruiting	Phase 1	45	Johnson & Johnson Enterprise Innovation Inc.INDUSTRY	3	Sep 25, 2026	clinicaltrials
NCT07271355	Pressurized Intraperitoneal Aerosolized Chemotherapy With Mitomycin for the Treatment of Unresectable Appendix or Colorectal Cancer With Peritoneal Metastases, The IMPACT Trial	recruiting	Phase 3	129	City of Hope Medical CenterOTHER	1	Sep 25, 2026	clinicaltrials
NCT07659795	A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer(TARGET-D 203)	recruiting	Phase 2	150	Verastem, Inc.INDUSTRY	2	Sep 25, 2026	clinicaltrials
NCT00295893	Combination Chemotherapy With or Without Trastuzumab in Treating Patients With Stage II or Stage III Breast Cancer	active not recruiting	Phase 2	121	City of Hope Medical CenterOTHER	1	Sep 24, 2026	clinicaltrials
NCT03573648	Neoadjuvant Endocrine Therapy, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer(ImmunoADAPT)	active not recruiting	Phase 2	33	Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsOTHER	1	Sep 24, 2026	clinicaltrials
NCT03716180	DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC	active not recruiting	Phase 1	100	Dana-Farber Cancer InstituteOTHER	1	Sep 24, 2026	clinicaltrials
NCT05863195	Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial	recruiting	Phase 3	408	ECOG-ACRIN Cancer Research GroupNETWORK	1	Sep 24, 2026	clinicaltrials
NCT06018337	A Study of DB-1303/BNT323 vs Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Metastatic Breast Cancer (DYNASTY-Breast02)	active not recruiting	Phase 3	541	DualityBio Inc.INDUSTRY	17	Sep 24, 2026	clinicaltrials
NCT06047379	Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis	recruiting	Phase 1 / Phase 2	134	Neonc Technologies, Inc.INDUSTRY	1	Sep 24, 2026	clinicaltrials
NCT06096844	Chemotherapy Combined With Immunotherapy Versus Immunotherapy Alone for Older Adults With Stage IIIB-IV Lung Cancer, The ACHIEVE Trial	recruiting	Phase 3	304	National Cancer Institute (NCI)NIH	1	Sep 24, 2026	clinicaltrials
NCT06123338	A Study of Pembrolizumab With Trastuzumab and Chemotherapy in People With Esophagogastric Cancer	recruiting	Phase 2	49	Memorial Sloan Kettering Cancer CenterOTHER	1	Sep 24, 2026	clinicaltrials
NCT07465757	A Study of Alisertib and Paclitaxel in Patients With Small Cell Lung Cancer (SCLC)(ALISCA-Lung2)	recruiting	Phase 2	50	Puma Biotechnology, Inc.INDUSTRY	1	Sep 24, 2026	clinicaltrials
NCT07839819	Study of PM54 in Combination With Cytotoxic and Targeted Agents in Adult Participants With Advanced Malignancies	not yet recruiting	Phase 1 / Phase 2	231	PharmaMarINDUSTRY	4	Sep 24, 2026	clinicaltrials
NCT02194738	Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)	active not recruiting	N/A	7,458	National Cancer Institute (NCI)NIH	3	Sep 23, 2026	clinicaltrials
NCT04400695	A Study of RC48-ADC for the Treatment of Locally Advanced or Metastatic Breast Cancer With Low Expression of HER2	recruiting	Phase 3	366	RemeGen Co., Ltd.INDUSTRY	1	Sep 23, 2026	clinicaltrials
NCT05489211	Study of Dato-DXd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)	recruiting	Phase 2	454	AstraZenecaINDUSTRY	14	Sep 23, 2026	clinicaltrials
NCT06102902	Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer	recruiting	Phase 1	30	National Cancer Institute (NCI)NIH	1	Sep 23, 2026	clinicaltrials
NCT06302621	Pemigatinib + Afatinib in Advanced Refractory Solid Tumors	recruiting	Phase 1	32	Massachusetts General HospitalOTHER	1	Sep 23, 2026	clinicaltrials
NCT03965689	Testing the Combination of MLN4924 (Pevonedistat), Carboplatin, and Paclitaxel in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) Who Have Previously Been Treated With Immunotherapy	active not recruiting	Phase 2	27	National Cancer Institute (NCI)NIH	1	Sep 22, 2026	clinicaltrials
NCT04928846	A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)	recruiting	Phase 3	768	AbbVieINDUSTRY	32	Sep 22, 2026	clinicaltrials
NCT05215548	Primary Tumor Resection With EGFR TKI for Stage IV NSCLC	recruiting	Phase 2	100	National Taiwan University HospitalOTHER	1	Sep 22, 2026	clinicaltrials
NCT06445062	Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors	recruiting	Phase 1 / Phase 2	1,130	Revolution Medicines, Inc.INDUSTRY	1	Sep 22, 2026	clinicaltrials
NCT06589804	Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment	recruiting	Phase 3	158	National Cancer Institute (NCI)NIH	1	Sep 22, 2026	clinicaltrials
NCT06712316	Safety, Efficacy, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer	recruiting	Phase 2 / Phase 3	1,580	BioNTech SEINDUSTRY	22	Sep 22, 2026	clinicaltrials
NCT07146646	Trifluridine/Tipiracil + Oxaliplatin in Participants With Advanced or Metastatic Biliary Tract Cancer	recruiting	Phase 2	27	Case Comprehensive Cancer CenterOTHER	1	Sep 22, 2026	clinicaltrials
NCT07409272	A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer	recruiting	Phase 3	614	Astellas Pharma Global Development, Inc.INDUSTRY	6	Sep 22, 2026	clinicaltrials
NCT07415031	A Solid Tumor Study for Long Term Treatment of Cancer Patients Who Participated in Adagrasib Studies	recruiting	Phase 2	170	Mirati Therapeutics Inc.INDUSTRY	20	Sep 22, 2026	clinicaltrials
NCT04543071	Chemo4METPANC Combination Chemokine Inhibitor, Immunotherapy, and Chemotherapy in Pancreatic Adenocarcinoma	active not recruiting	Phase 2	118	Columbia UniversityOTHER	1	Sep 21, 2026	clinicaltrials
NCT04644068	Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies(PETRA)	active not recruiting	Phase 1 / Phase 2	702	AstraZenecaINDUSTRY	14	Sep 21, 2026	clinicaltrials

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

Approval rows flagged tumor-agnostic (2)

Associated cancers (22)

Drugs with predictive evidence (27)

Predictive evidence items (71)

Approvals mentioning the linked drugs (500)

Active trials (957)

Linked publications (63)