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| Gene | ERBB2 |
| Variant | positive |
| Impact List | unknown |
| Protein Effect | unknown |
| Gene Variant Descriptions | ERBB2 (HER2) positive indicates the presence of the ERBB2 (HER2) gene, mRNA, and/or protein. ERBB2 (HER2) positive has been used alternatively to refer to overexpression and/or amplification of ERBB2 (HER2). For related data, refer to ERBB2 amp or ERBB2 over exp in CKB. |
| Associated Drug Resistance |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Trastuzumab deruxtecan | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Enhertu (fam-trastuzumab deruxtecan-nxki) inhibited growth of ERBB2 (HER2)-positive breast cancer cell lines in culture and xenograft models, and demonstrated antitumor activity in patient-derived xenograft (PDX) models of ERBB2 (HER2)-positive breast cancer, including models with low ERBB2 (HER2) expression (PMID: 27026201). | 27026201 |
| ERBB2 positive | stomach cancer | predicted - sensitive | Margetuximab-cmkb | Phase I | Actionable | In a Phase I trial, Margenza (margetuximab-cmkb) treatment resulted in partial responses in 12% (7/60) and stable disease in 50% (30/60) of patients with ERBB2 (HER2)-positive breast or gastric cancer, or other carcinomas that overexpress Erbb2 (Her2) (PMID: 28119295; NCT01148849). | 28119295 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | MM-302 | Phase I | Actionable | In a Phase I study, MM-302 demonstrated safety in patients with ERBB2 (HER2) positive breast cancer (Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-09) | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | SB3 | Phase III | Actionable | In a Phase III trial, SB3 treatment demonstrated safety, immunogenicity, and survival result similar to Herceptin (trastuzumab), resulted in event-free-survival rates of 92.2% and 91.6%, respectively, in patients with Erbb2 (Her2)-positive breast cancer (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 153PD; NCT02149524). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | ARX-788 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, treatment with ARX-788 led to greater sensitivity compared to Kadcyla (ado-trastuzumab emtansine) in breast cancer cell lines with ERBB2 (HER2) expression in culture, and stronger tumor growth inhibition in breast cancer cell line xenograft models and patient-derived xenograft (PDX) models with ERBB2 (HER2) expression (PMID: 32669315). | 32669315 |
| ERBB2 positive | breast cancer | predicted - sensitive | Timigutuzumab | Case Reports/Case Series | Actionable | In a Phase I trial, Timigutuzumab treatment demonstrated safety and tolerability, and resulted in a partial response in one and stable disease in four ERBB2 (HER2)-positive breast cancer patients (n=7) previously treated with Herceptin (trastuzumab), and in the patient with a partial response, led to a 73% reduction in tumor size following 62 days of treatment that lasted for 113 days (PMID: 30018811; NCT01409343). | 30018811 |
| ERBB2 positive | breast cancer | sensitive | Withacnistin | Preclinical | Actionable | In a preclinical study, withacnistin induced tumor regression in transgenic mouse models of Erbb2 (Her2)-driven breast cancer (PMID: 24983364). | 24983364 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Oxaliplatin + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Herceptin (trastuzumab) and Eloxatin (oxaliplatin) resulted in growth inhibition of ERBB2 (HER2)-positive breast cancer cells in culture (PMID: 24300914). | 24300914 |
| ERBB2 positive | pancreatic cancer | sensitive | Trastuzumab deruxtecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Enhertu (fam-trastuzumab deruxtecan-nxki) inhibited tumor growth in a pancreatic cancer cell line xenograft model with low ERBB2 (HER2) expression (PMID: 27026201). | 27026201 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Capecitabine + Pyrotinib | Phase I | Actionable | In a Phase I trial, Pyrotinib and Xeloda (capecitabine) combination treatment was well-tolerated, and resulted in an overall response rate of 78.6% (22/28) in patients with Erbb2 (Her2)-positive metastatic breast cancer, with a median progression-free survival of 22.1 months (PMID: 31138588; NCT02361112). | 31138588 |
| ERBB2 positive | gastroesophageal junction adenocarcinoma | no benefit | MM-111 + Paclitaxel + Trastuzumab | Phase II | Actionable | In a Phase II trial, Taxol (paclitaxel) and Herceptin (trastuzumab) treatment in combination with MM-111 did not improve progression free survival (9.6 weeks) and median overall survival (32.1 weeks) compared to without MM-111 (23.3 weeks, 56.1 weeks) in ERBB2 positive gastroesophageal junction cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 4043)). | detail... |
| ERBB2 positive | stomach cancer | predicted - sensitive | MEDI4276 | Phase I | Actionable | In a Phase I trial, MEDI4276 treatment resulted in complete response in 1 patient with breast cancer, partial response in 1 patient with breast cancer, and stable disease in 12 patients with Erbb2 (Her2)-positive breast or gastric cancer (Annals of Oncology, Volume 29, Issue suppl_3, 1 March 2018, abstract 470; NCT02576548). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Cyclophosphamide + Doxorubicin + Paclitaxel + Pertuzumab + Trastuzumab | Guideline | Actionable | Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab) and Perjeta (pertuzumab), is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). | detail... |
| ERBB2 positive | stomach cancer | sensitive | Oxaliplatin + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Herceptin (trastuzumab) and Eloxatin (oxaliplatin) resulted in growth inhibition of ERBB2 (HER2)-positive gastric cancer cells in culture (PMID: 24300914). | 24300914 |
| ERBB2 positive | transitional cell carcinoma | predicted - sensitive | Disitamab vedotin | Phase II | Actionable | In a Phase II trial, Disitamab vedotin (RC48) demonstrated safety and resulted in an objective response rate of 51.2% (22/43, all partial responses), disease control rate of 90.7% (39/43), median progression-free survival of 6.9 months, and median overall survival of 13.9 months in patients with ERBB2 (HER2)-positive (IHC = 3+ or 2+) advanced or metastatic urothelial carcinoma who had failed prior chemotherapy (PMID: 33109737; NCT03507166). | 33109737 |
| ERBB2 positive | esophageal cancer | predicted - sensitive | Afatinib + Trastuzumab | Phase II | Actionable | In a Phase II clinical trial, the combination therapy of Gilotrif (afatinib) and Herceptin (trastuzumab) in ERBB2 (HER2)-positive patients with either gastroesophageal junction adenocarcinoma, metastatic esophageal cancer, or gastric adenocarcinoma resulted in a partial response in 8% (1/12) and disease control for 4 months or more in 17% (2/12) (PMID: 30463996; NCT01522768). | 30463996 |
| ERBB2 positive | gastroesophageal adenocarcinoma | predicted - sensitive | GBR1302 | Case Reports/Case Series | Actionable | In a Phase I trial, GBR 1302 treatment resulted in prolonged (more than 4 months) stable disease in a patient with ERBB2 (HER2) positive (IHC 3+) gastroesophageal adenocarcinoma (Annals of Oncology, Volume 29, Issue suppl_8, October 2018, mdy288.020; NCT02829372). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Ado-trastuzumab emtansine + Tucatinib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination of Tukysa (tucatinib) and Trastuzumab emtansine (T-DM1) demonstrated clinical activity in CNS metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 12.5% (1/8) evaluable patients achieving CNS complete response, 25% (2/8) partial CNS response, and 62.5% (5/8) CNS stable disease (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Ado-trastuzumab emtansine + Tucatinib | Phase Ib/II | Actionable | In a Phase Ib clinical trial, treatment with the combination of Tukysa (tucatinib) and Trastuzumab emtansine (T-DM1) resulted in partial response in 33% (11/33) and stable disease in 48% (16/33) and a clinical benefit rate of 58% (19/33) in patients with ERBB2 (HER2)-positive metastatic breast cancer (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-20). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Ado-trastuzumab emtansine + Tucatinib | Phase Ib/II | Actionable | In a Phase Ib clinical trial, treatment with the combination of Tucatinib (ARRY-380) and Trastuzumab emtansine (T-DM1) resulted in an overall response rate of 47% (15/52) and median progression-free survival of 6.5 months in patients with ERBB2 (HER2)-positive metastatic breast cancer, including patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 513)). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | no benefit | Trastuzumab + Vinorelbine | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Herceptin (trastuzumab) and Navelbine (vinorelbine) resulted in a 0% objective response rate in pretreated ERBB2 (HER2)-receptor positive breast cancer patients (N=5) (PMID: 31892325). | 31892325 |
| ERBB2 positive | Advanced Solid Tumor | predicted - sensitive | Trastuzumab deruxtecan | Phase I | Actionable | In a Phase I trial, treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) demonstrated safety in patients with non-breast/non-gastric ERBB2 (HER2)-expressing or ERBB2 (HER2)-mutant solid tumors and resulted in an objective response rate of 28.3% (17/60), median duration of response of 11.5 months, median progression-free survival of 7.2 months, and median overall survival of 23.4 months (PMID: 32213540; NCT02564900). | 32213540 |
| ERBB2 positive | stomach cancer | sensitive | Trastuzumab deruxtecan | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Enhertu (fam-trastuzumab deruxtecan-nxki) inhibited growth of a ERBB2 (HER2)-positive gastric carcinoma cell line in culture and in xenograft models, and induced tumor regression in a patient-derived xenograft (PDX) model of ERBB2 (HER2)-positive gastric cancer (PMID: 27026201). | 27026201 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | HER2 BATs | Preclinical - Cell culture | Actionable | In a preclinical study, HER2 BATs demonstrated enhanced toxicity comparing to unarmed T-cells against Erbb2 (Her2)-positive breast cancer cells in culture (PMID: 11359672). | 11359672 |
| ERBB2 positive | Advanced Solid Tumor | predicted - sensitive | GBR1302 | Phase I | Actionable | In a Phase I trial, GBR 1302 treatment resulted in no radiological response, only prolonged (more than 4 months) stable disease in 10.5% (2/19) of patients with ERBB2 (HER2) positive advanced solid tumors (Annals of Oncology, Volume 29, Issue suppl_8, October 2018, mdy288.020; NCT02829372). | detail... |
| ERBB2 positive | gastroesophageal junction adenocarcinoma | predicted - sensitive | Afatinib + Trastuzumab | Phase II | Actionable | In a Phase II clinical trial, the combination therapy of Gilotrif (afatinib) and Herceptin (trastuzumab) in ERBB2 (HER2)-positive patients with either gastroesophageal junction adenocarcinoma, metastatic esophageal cancer, or gastric adenocarcinoma resulted in a partial response in 8% (1/12) and disease control for 4 months or more in 17% (2/12) (PMID: 30463996; NCT01522768). | 30463996 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine + Docetaxel | Phase Ib/II | Actionable | In a Phase Ib/II trial, Kadcyla (trastuzumab emtansine) and Taxotere (docetaxel) combination treatment resulted in median progression-free survival of 13.8 months and objective response in 80.0% (20/25) of patients with ERBB2 (HER2)-positive metastatic breast cancer (PMID: 27052654). | 27052654 |
| ERBB2 positive | breast cancer | predicted - sensitive | BAT8001 | Phase I | Actionable | In a Phase I trial, BAT8001 was well tolerated, and resulted in a complete response in 3.7% (1/27), a partial response in 18.5 % (5/27), and stable disease in 18.5% (5/27) of ERBB2 (HER2)-positive breast cancer patients following 10 months of treatment (Cancer Res 2019;79(13 Suppl):Abstract nr CT053). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine + Docetaxel + Pertuzumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, Kadcyla (trastuzumab emtansine), Taxotere (docetaxel) and Perjeta (pertuzumab) combination treatment resulted in pathologic complete response in 60.3% (44/73) of patients with ERBB2 (HER2)-positive locally advanced breast cancer (PMID: 27052654). | 27052654 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Carboplatin + Docetaxel + Trastuzumab | Guideline | Actionable | Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) therapy is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Capecitabine + Neratinib | Phase II | Actionable | In a Phase II trial, Nerlynx (neratinib) and Xeloda (capecitabine) combination therapy resulted in an overall 12-month survival rate of 63% (23/37) in patients with Erbb2 (Her2)-positive breast cancer brain metastases (J Clin Oncol 35, 2017 (suppl; abstr 1005)). | detail... detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | CDX-3379 | Preclinical | Actionable | In a preclinical study, CDX-3379 (KTN3379) inhibited tumor growth in xenograft models of ERBB2 (HER2)-positive breast cancer (PMID: 26880266). | 26880266 |
| ERBB2 positive | gastric adenocarcinoma | predicted - sensitive | Afatinib | Phase II | Actionable | In a Phase II clinical trial, monotherapy with Gilotrif (afatinib) resulted in a moderate clinical benefit in ERBB2 (HER2)-positive patients with either gastroesophageal junction adenocarcinoma, metastatic esophageal cancer, or gastric adenocarcinoma, demonstrating a tumor reduction in 25% (5/20) according to RECIST, an objective partial response in 10% (2/20), a median progression-free survival of 2 months, and a median overall survival of 7 months (PMID: 30463996; NCT01522768). | 30463996 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | GBR1302 | Case Reports/Case Series | Actionable | In a Phase I trial, GBR 1302 treatment resulted in prolonged (more than 4 months) stable disease in a patient with ERBB2 (HER2) positive (IHC 2+) breast adenocarcinoma (Annals of Oncology, Volume 29, Issue suppl_8, October 2018, mdy288.020; NCT02829372). | detail... |
| ERBB2 positive | glioblastoma | sensitive | HER2 CAR-T cells | Phase I | Actionable | In a Phase I trial, glioblastoma patients positive for ERBB2 (HER2) demonstrated antitumor activity when treated with ERBB2 (HER2)-CAR-T cell therapy including one patient with a partial response and seven patients with stable disease ranging from 8 weeks to 29 months (PMID: 28426845). | 28426845 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Margetuximab-cmkb + MGD013 | Case Reports/Case Series | Actionable | In a Phase I trial, MGD013 and Margenza (margetuximab-cmkb) combination treatment resulted in a partial response in 2 patients with ERBB2 (HER2)-positive breast cancer (J Clin Oncol 38: 2020 (suppl; abstr 3004); NCT03219268). | detail... |
| ERBB2 positive | Advanced Solid Tumor | predicted - sensitive | Epertinib | Phase I | Actionable | In a Phase I clinical trial, S-222611 demonstrated safety and some efficacy in patients with advanced solid tumors expressing EGFR or ERBB2 (HER2), with an overall clinical benefit rate of 27% (7/33) (PMID: 25434923). | detail... 25434923 |
| ERBB2 positive | esophageal cancer | predicted - sensitive | Afatinib | Phase II | Actionable | In a Phase II clinical trial, monotherapy with Gilotrif (afatinib) resulted in a moderate clinical benefit in ERBB2 (HER2)-positive patients with either gastroesophageal junction adenocarcinoma, metastatic esophageal cancer, or gastric adenocarcinoma, demonstrating a tumor reduction in 25% (5/20) according to RECIST, an objective partial response in 10% (2/20), a median progression-free survival of 2 months, and a median overall survival of 7 months (PMID: 30463996; NCT01522768). | 30463996 |
| ERBB2 positive | ovarian carcinoma | sensitive | ADC ST8176AA1 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ADC ST8176AA1 treatment induced apoptosis and inhibited proliferation of ERBB2 (HER2) expressing ovary carcinoma cells in culture, and inhibited tumor growth, and increased median survival in cell line xenograft models (PMID: 32039017). | 32039017 |
| ERBB2 positive | colorectal cancer | no benefit | ZW25 | Phase I | Actionable | In a Phase I trial, ZW25 treatment resulted in disease progression in a patient with ERBB2 (HER2)-positive colorectal cancer (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 255P; NCT02892123). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | no benefit | Ado-trastuzumab emtansine + Capecitabine | Phase II | Actionable | In a Phase II trial, the combination therapy of Xeloda (capecitabine) and Kadcyla (ado-trastuzumab emanstine) resulted in increased toxicity and did not lead to improved clinical benefit compared to Kadcyla (ado-trastuzumab emanstine)as a single agent in ERBB2 (HER2)-positive breast cancer patients, with an overall response rate of 44% (36/81) versus 36% (29/80; P=0.34), respectively (PMID: 32584367; NCT01702558). | 32584367 |
| ERBB2 positive | breast cancer | predicted - sensitive | MP0274 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MP0274 inhibited proliferation of Erbb2 (Her2)-positive breast cancer cells in culture and induced tumor regression in cell line xenograft models (Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-30). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Disitamab vedotin | Preclinical - Cell culture | Actionable | In a preclinical study, Hertuzumab-vc-MMAE decreased viability of ERBB2 (HER2)-positive breast cancer cell lines in culture (PMID: 27509865). | 27509865 |
| ERBB2 positive | gastroesophageal cancer | predicted - sensitive | Margetuximab-cmkb + Pembrolizumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Margenza (margetuximab-cmkb) and Keytruda (pembrolizumab) demonstrated safety and tolerability with an objective response rate of 18.5% (17/92), median progression-free survival of 2.73 months, and median overall survival of 12.48 months in patients with ERBB2 (HER2)-positive gastroesophogeal adenocarcinoma (PMID: 32653053; NCT02689284). | 32653053 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Everolimus + Trastuzumab + Vinorelbine | Phase III | Actionable | In a Phase III trial (BOLERO-3), the combination of Afinitor (everolimus), Herceptin (trastuzumab), and Navelbine (vinorelbine) increased progression-free survival in patients with Herceptin (trastuzumab)-resistant, ERBB2 (HER2)-positive, advanced breast cancer who had prior taxane treatment (PMID: 24742739; NCT01007942). | 24742739 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Buparlisib + Trastuzumab | Phase I | Actionable | In a Phase I clinical trial, the combination of Buparlisib (BKM120) and Herceptin (trastuzumab) was well tolerated in patients with ERBB2 (HER2)-positive advanced or metastatic breast cancer that had progressed on Herceptin (trastuzumab) (PMID: 24470511). | 24470511 |
| ERBB2 positive | stomach carcinoma | sensitive | Tucatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tukysa (tucatinib) inhibited tumor growth in a ERBB2 (HER2)-positive gastric carcinoma cell line xenograft model (Cancer Res April 15, 2012 72:852). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Capecitabine + Tucatinib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination of Tukysa (tucatinib) with other agents demonstrated clinical activity in central nervous system (CNS) metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 1/1 evaluable patient treated with Tucatinib (ARRY-380) and Capecitabine achieving CNS partial response (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | ZW25 | Phase I | Actionable | In a Phase I trial, ZW25 treatment resulted in partial response in 28.6% (2/7) and stable disease in 28.6% (2/7) of patients with ERBB2 (HER2)-positive breast cancers (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 255P; NCT02892123). | detail... |
| ERBB2 positive | breast cancer | sensitive | XMT-1522 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XMT-1522 demonstrated improved efficacy compared to Kadcyla (ado-trastuzumab emtansine), inhibited growth of Erbb2 (Her2)-positive breast cancer cells in culture, resulted in tumor regression and prolonged survival in cell line xenograft models (PMID: 31292166). | 31292166 |
| ERBB2 positive | breast cancer | sensitive | Ado-trastuzumab emtansine + Tucatinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, ERBB2 (HER2)-positive breast cancer patients demonstrated an objective response rate of 47% (16/34), including one complete response and fifteen partial responses, and a progression-free survival of 8.2 months when treated with a combination of Tukysa (tucatinib) and Kadcyla (trastuzumab emtansine) compared to 6.5 months with Herceptin (trastuzumab) and Perjeta (pertuzumab) treatment (PMID: 29955792; NCT01983501). | 29955792 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Capecitabine + Trastuzumab + Tucatinib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination of Tukysa (tucatinib), Herceptin (trastuzumab), and Capecitabine demonstrated clinical activity in CNS metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 50% (1/2) of evaluable patients achieving CNS partial response and 50% (1/2) achieving CNS stable disease (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Neratinib | Phase II | Actionable | In a Phase II clinical trial, Nerlynx (neratinib) demonstrated safety and efficacy as a monotherapy in patients with ERBB2 (HER2)-positive breast cancer (PMID: 23953056). | 23953056 |
| ERBB2 positive | ovarian cancer | sensitive | ARX-788 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, an ERBB2 (HER2)-positive ovarian cancer xenograft model was sensitive to treatment with ARX-788, resulting in tumor regression (Cancer Res 2015;75(15 Suppl):Abstract nr 639). | detail... |
| ERBB2 positive | Advanced Solid Tumor | predicted - sensitive | MT-5111 | Preclinical - Cell culture | Actionable | In a preclinical study, MT-5111 demonstrated toxicity against Erbb2 (Her2) positive tumor cell lines in culture regardless of their sensitivity to Kadcyla (ado-trastuzumab emtansine) (Cancer Res 2018;78(13 Suppl):Abstract nr 5769). | detail... |
| ERBB2 positive | breast carcinoma | sensitive | Trastuzumab Duocarmazine | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Trastuzumab Duocarmazine (SYD985) decreased survival of ERBB2 (HER2)-positive breast carcinoma cell lines in culture, and inhibited tumor growth and induced tumor remission in cell line and patient-derived xenograft models of ERBB2 (HER2)-positive breast carcinoma, including models with low ERBB2 (HER2) expression (PMID: 25589493). | 25589493 |
| ERBB2 positive | stomach cancer | sensitive | MI130004 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MI130004 inhibited proliferation of ERBB2 (HER2)-positive gastric cancer cells in culture, and led to decreased tumor volume and improved survival in cell line xenograft models (PMID: 29440297). | 29440297 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | MEDI4276 | Phase I | Actionable | In a Phase I trial, MEDI4276 treatment resulted in complete response in 1 patient with breast cancer, partial response in 1 patient with breast cancer, and stable disease in 12 patients with Erbb2 (Her2)-positive breast or gastric cancer (Annals of Oncology, Volume 29, Issue suppl_3, 1 March 2018, abstract 470; NCT02576548). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Lapatinib + Trastuzumab | Phase II | Actionable | In a Phase II trial, Tykerb (lapatinib) and Herceptin (trastuzumab) combination treatment resulted in complete response in the breast in 10.6% (7/66) and minimal residual disease in 16.7% (11/66) of ERBB2-positive breast cancer patients 11 days after receiving the treatment (European Breast Cancer Conference; Mar 2016; Abstract #6LBA). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Lapatinib + Trastuzumab | Clinical Study - Meta-analysis | Actionable | In a meta-analysis of six randomized clinical trials, Tykerb (lapatinib) and Herceptin (trastuzumab) combination treatment resulted in 13% absolute improvement in pathologic complete response rate in ERBB2 (HER2)-positive breast cancer patients compared to Herceptin (trastuzumab) single treatment (PMID: 27140927). | 27140927 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | HER2 Vaccine | Phase II | Actionable | In Phase II clinical trials, ERBB2 (HER2) vaccines demonstrated safety and some efficacy in the adjuvant setting in ERBB2 (HER2)-positive breast cancer patients (PMID: 23585514). | 23585514 |
| ERBB2 positive | ovarian cancer | sensitive | Disitamab vedotin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with Hertuzumab-vc-MMAE decreased viability of ERBB2 (HER2)-positive ovarian cancer cell lines in culture and inhibited tumor growth in ERBB2 (HER2)-positive ovarian cancer cell line xenograft models (PMID: 27509865). | 27509865 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Abemaciclib + Fulvestrant + Trastuzumab | Phase II | Actionable | In a Phase II trial, the combination therapy of Verzenio (abemaciclib), Herceptin (trastuzumab), and Faslodex (fulvestrant) in patients with ERBB2 (HER2)-receptor positive breast cancer (n=79) resulted in safety and a greater progression-free survival (PFS) compared to patients treated with standard of care chemotherapy plus Herceptin (trastuzumab) (n=79), demonstrating a PFS of 8.3 months versus 5.7 months (p=0.051), respectively (PMID: 32353342; NCT02675231). | 32353342 |
| ERBB2 positive | ovarian cancer | sensitive | PRS-343 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PRS-343 induced localized immune activation in cell line xenograft models of Erbb2 (Her2)-positive ovarian cancer, resulted in significant tumor growth inhibition (Eur J Cancer, Dec 2016, 69 (Suppl. 1): S99, abstract 301). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Margetuximab-cmkb | Phase I | Actionable | In a Phase I trial, Margenza (margetuximab-cmkb) treatment resulted in tumor reduction in 78% (18/23) of patients with ERBB2 (HER2)-positive breast cancer (PMID: 28119295; NCT01148849). | 28119295 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Pertuzumab + Trastuzumab | Phase III | Actionable | In a Phase III trial, adjuvant Herceptin (trastuzumab), Perjeta (pertuzumab), plus chemotherapy resulted in improved invasive disease-free survival compared to Herceptin (trastuzumab) plus chemotherapy in patients with Erbb2 (Her2)-positive breast cancer (J Clin Oncol 35, 2017 (suppl; abstr LBA500)). | detail... |
| ERBB2 positive | inflammatory breast carcinoma | predicted - sensitive | Afatinib | Phase II | Actionable | In a Phase II clinical trial, treatment with Gilotrif (afatinib) resulted in a clinical benefit rate of 35% (9/26) in patients with ERBB2 (HER2)-positive inflammatory breast cancer, with 8 confirmed partial responses and 1 patient achieving stable disease for greater than 6 months (PMID: 27923043). | 27923043 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | MBS301 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MBS301 inhibited proliferation of ERBB2 (HER2)-positive breast cancer cell lines expressing high or low levels of ERBB2 (HER2) in culture, and inhibited tumor growth in xenograft models (PMID: 30081724). | 30081724 |
| ERBB2 positive | Advanced Solid Tumor | sensitive | Timigutuzumab | Phase I | Actionable | In a Phase I study, Timigutuzumab treatment was well-tolerated and demonstrated safety, and resulted in a clinical benefit in 50% (1 complete response, 2 partial response, and 12 stable disease), a disease control rate of 50%, and an objective response rate of 10% in ERBB2 (HER2)-positive advanced solid tumor patients (n=30) (PMID: 30018811; NCT01409343). | 30018811 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Sunitinib + Trastuzumab | Phase II | Actionable | In a Phase II trial, Sutent (sunitinib), in combination with Herceptin (trastuzumab), demonstrated safety and efficacy in ERBB2 (HER2) positive advanced breast cancer patients (PMID: 24606768). | 24606768 |
| ERBB2 positive | Advanced Solid Tumor | predicted - sensitive | ZW25 | Phase I | Actionable | In a Phase I trial, ZW25 treatment resulted in partial response in 14% (2/14) and stable disease in 21% (3/14) of patients with ERBB2 (HER2)-positive tumors, including breast, gastric, esophageal, colorectal, and adnexal cancers (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 255P; NCT02892123). | detail... |
| ERBB2 positive | breast cancer | sensitive | ZW49 | Preclinical - Pdx | Actionable | In a preclinical study, ZW49 treatment induced tumor regression in patient-derived xenograft (PDX) models of breast cancer expressing low and high levels of ERBB2 (HER2) (Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-13). | detail... |
| ERBB2 positive | stomach carcinoma | sensitive | Trastuzumab Duocarmazine | Preclinical - Cell culture | Actionable | In a preclinical study, Trastuzumab Duocarmazine (SYD985) decreased survival of a ERBB2 (HER2)-positive gastric carcinoma cell line in culture (PMID: 25589493). | 25589493 |
| ERBB2 positive | breast adenocarcinoma | sensitive | Trastuzumab deruxtecan | Preclinical - Cell culture | Actionable | In a preclinical study, Enhertu (fam-trastuzumab deruxtecan-nxki) inhibited growth of an ERBB2 (HER2)-positive breast adenocarcinoma cell line in culture (PMID: 27026201). | 27026201 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Cyclophosphamide + Doxorubicin + Paclitaxel + Trastuzumab | Guideline | Actionable | Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab), is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 positive | gastroesophageal junction adenocarcinoma | no benefit | Ado-trastuzumab emtansine | Phase III | Actionable | In a Phase III trial (GATSBY), Kadcyla (trastuzumab emtansine) did not demonstrate efficacy benefit over Taxol (paclitaxel) in median overall survival (7.9 vs 8.6 months) in patients with previously treated ERBB2 (HER2)-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (PMID: 28343975; NCT01641939). | detail... 28343975 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Phase III | Actionable | In a Phase III trial, Kadclya (trastuzumab emtansine) demonstrated improved median progression free survival and overall survival compared to Tykerb (lapatinib) and Xeloda (capecitabine) combination treatment in patients with ERBB2 (HER2) positive breast cancer, regardless of the expression level of Erbb2 (Her2), Egfr, and Her3, or PIK3CA mutation status (PMID: 26920887). | 26920887 |
| ERBB2 positive | colon carcinoma | sensitive | ADC ST8176AA1 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ADC ST8176AA1 treatment reversed epithelial to mesenchymal (EMT) transition, induced DNA damage, increased apoptosis, and inhibited Erbb2 (Her2) signaling and proliferation of ERBB2 (HER2) expressing colon carcinoma cells in culture, and increased median survival in a cell line xenograft model (PMID: 32039017). | 32039017 |
| ERBB2 positive | transitional cell carcinoma | no benefit | lapuleucel-T | Phase II | Actionable | In a Phase II trial, Neuvenge (lapuleucel-T) treatment did not result in statistically significant improvement of overall survival (37.0 vs 22.2 months, HR = 0.96) or disease recurrence-free survival (11.9 vs 10.1 months, HR = 0.99) compared to standard of care in ERBB2 (HER2) positive urothelial cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 4513)). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Metformin | Phase III | Actionable | In a Phase III trial, ERBB2 (HER2) positive breast cancer patients with diabetes demonstrated a greater disease free survival and overall survival when treated with Glucophage (metformin) compared to ERBB2 (HER2) positive breast cancer patients with diabetes not treated with Glucophage (metformin) (PMID: 28375706). | 28375706 |
| ERBB2 positive | stomach cancer | sensitive | ARX-788 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, an ERBB2 (HER2)-positive gastric cancer xenograft model was sensitive to treatment with ARX-788, resulting in a 90% tumor growth inhibition at the highest dose (PMID: 32669315). | 32669315 |
| ERBB2 positive | ovarian cancer | sensitive | MI130004 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MI130004 inhibited proliferation of ERBB2 (HER2)-positive ovarian cancer cells in culture, and led to decreased tumor volume, reduced ERBB2 (HER2) expression, and improved survival in cell line xenograft models (PMID: 29440297). | 29440297 |
| ERBB2 positive | endometrial serous adenocarcinoma | sensitive | Trastuzumab Duocarmazine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Trastuzumab Duocarmazine (SYD895) induced cell death in ERBB2 (HER2)-expressing primary uterine serous carcinoma (USC) cell lines in culture, including cell lines with both high and low levels of ERBB2 (HER2) expression, and inhibited tumor growth and improved survival in ERBB2 (HER2)-expressing USC primary cell line xenografts (PMID: 27256376). | 27256376 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Neratinib + Paclitaxel | Phase II | Actionable | In a Phase II trial, Nerlynx (neratinib) plus Taxol (paclitaxel) demonstrated similar efficacy to Herceptin (trastuzumab) plus Taxol (paclitaxel), with an median progression-free survival of 12.9 months, however, potentially decreased CNS metastasis risk, with an incidence of 8.3% (20/242) compared to 17.3% (41/237) in the Herceptin (trastuzumab) plus Taxol (paclitaxel) group (PMID: 27078022). | 27078022 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Afatinib + Trastuzumab | Phase I | Actionable | In a Phase I clinical trial, ERBB2 (HER2)-positive breast cancer patients treated with Gilotrif (afatinib), in combination with Herceptin (trastuzumab), demonstrated an overall objective response rate of 11% (2/18) while 28% (5/18) attained a best response of stable disease (PMID: 25370464). | 25370464 |
| ERBB2 positive | salivary gland cancer | predicted - sensitive | Trastuzumab deruxtecan | Phase I | Actionable | In a Phase I trial, treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) in patients with non-breast/non-gastric ERBB2 (HER2)-expressing or ERBB2 (HER2)-mutant solid tumors resulted in an objective response rate of 27.3% (6/22) and median progression-free survival of 11.0 months in the subgroup with cancers other than non-small cell lung cancer or colorectal cancer, including responses among patients with ERBB2 (HER)-expressing or amplified salivary gland cancer (PMID: 32213540; NCT02564900). | 32213540 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Trastuzumab + Tucatinib | Phase Ib/II | Actionable | In a Phase Ib clinical trial, the combination of Tukysa (tucatinib) and Herceptin (trastuzumab) demonstrated clinical activity in central nervous system (CNS) metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 100% (3/3) patients achieving CNS stable disease as best response (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Oxaliplatin + Tegafur-gimeracil-oteracil Potassium + Trastuzumab | Phase II | Actionable | In a Phase II clinical trial, the combination of TS-1 (S-1) and Herceptin (trastuzumab) demonstrated safety and efficacy in patients with ERBB2 (HER2)-positive metastatic breast cancer, with an overall response rate of 53.6% (15/28), and a clinical benefit rate of 75.0% (21/28) (PMID: 24982373). | 24982373 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Lapatinib + Palbociclib | Preclinical | Actionable | In a preclinical study, the combination of Tykerb (lapatinib) and Ibrance (palbociclib) worked additively to suppress growth of ERBB2 (HER2)-positive breast cancer cell lines in culture (PMID: 25221644). | 25221644 |
| ERBB2 positive | Advanced Solid Tumor | predicted - sensitive | AC480 | Phase I | Actionable | In a Phase I clinical trial, AC480 (BMS-599626) treatment demonstrated preliminary clinical activity, resulting in stable disease as best response in 25% (11/44) of patients with advanced solid tumors, including patients expressing EGFR and/or ERBB2, with 2 patients achieving stable disease for greater than 6 months (PMID: 21576284). | 21576284 |
| ERBB2 positive | endometrial serous adenocarcinoma | sensitive | Carboplatin + Paclitaxel + Trastuzumab | Guideline | Actionable | Combination Paraplatin (carboplatin), Taxol (paclitaxel), and Herceptin (trastuzumab) is in guidelines for ERBB2 (HER2)-positive patients with advanced and recurrent uterine serous carcinoma (NCCN.org). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Pyrotinib | Phase I | Actionable | In a Phase I trial, Pyrotinib treatment resulted in an objective response rate of 50% (18/36, all partial responses), and a clinical benefit rate of 61.1% (22/36), and a median progression-free survival of 35.4 weeks in patients with ERBB2 (HER2)-positive breast cancer (PMID: 28498781, NCT01937689). | detail... 28498781 |
| ERBB2 positive | salivary gland cancer | predicted - sensitive | Timigutuzumab | Case Reports/Case Series | Actionable | In a Phase I trial, Timigutuzumab resulted in elimination of a tumor lesion following 178 days of treatment in an ERBB2 (HER2)-positive salivary duct carcinoma patient, and led to a complete remission that was ongoing for 53 months (PMID: 30018811; NCT01409343). | 30018811 |
| ERBB2 positive | stomach cancer | sensitive | XMT-1522 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XMT-1522 demonstrated improved efficacy compared to Kadcyla (ado-trastuzumab emtansine), inhibited growth of Erbb2 (Her2)-positive gastric cancer cell lines in culture, resulted in tumor regression and prolonged survival in cell line xenograft models (PMID: 31292166). | 31292166 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Carboplatin + Docetaxel + Pertuzumab + Trastuzumab | Guideline | Actionable | Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) plus Perjeta (pertuzumab) therapy, is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Epertinib + Trastuzumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination therapy of Epertinib (S-222611) and Herceptin (trastuzumab) resulted in an objective response rate of 67% (6/9) in pretreated ERBB2 (HER2)-receptor positive breast cancer patients, including 6 patients with a partial response (PMID: 31892325). | 31892325 |
| ERBB2 positive | Advanced Solid Tumor | predicted - sensitive | Margetuximab-cmkb + MGD013 | Phase I | Actionable | In a Phase I trial, MGD013 and Margenza (margetuximab-cmkb) combination treatment resulted in a partial response in 50% (3/6) and stable disease in 33.3% (2/6) of patients with ERBB2 (HER2)-positive advanced solid tumors (J Clin Oncol 38: 2020 (suppl; abstr 3004); NCT03219268). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Capecitabine + Trastuzumab | Phase II | Actionable | In Phase II clinical trials, the combination of Xeloda (capecitabine) and Herceptin (trastuzumab) demonstrated efficacy with a manageable toxicity profile in heavily pretreated patients with ERBB2 (HER2)-positive advanced breast cancer and earlier Herceptin (trastuzumab) exposure (PMID: 17679724). | 17679724 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Capecitabine + Trastuzumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination therapy of Herceptin (trastuzumab) and Xeloda (capecitabine) resulted in an objective response rate of 56% (5/9) in pretreated ERBB2 (HER2)-receptor positive breast cancer patients, including 5 patients with a partial response (PMID: 31892325). | 31892325 |
| ERBB2 positive | lung non-small cell carcinoma | predicted - sensitive | Trastuzumab deruxtecan | Phase I | Actionable | n a Phase I trial, treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) in patients with ERBB2 (HER2)-expressing or ERBB2 (HER2)-mutant non-small cell lung cancer resulted in an objective response rate of 55.6% (10/18), median duration of response o 10.7 months, and median progression-free survival of 11.3 months (PMID: 32213540; NCT02564900). | 32213540 |
| ERBB2 positive | breast cancer | no benefit | Nelipepimut-S Plus GM-CSF | Phase III | Actionable | In a Phase III trial, breast cancer patients with low expression of ERBB2 (HER2) (IHC 1+/2+, FISH negative) treated with Nelipepimut-S plus GM-CSF (n=372) did not demonstrate a significant difference in disease-free survival events (HR=1.564, p=0.069) compared to patients who received placebo plus GM-CSF (n=373) at the median follow-up time point of 16.8 months, leading to early termination of the clinical trial (PMID: 31036542; NCT01479244). | 31036542 |
| ERBB2 positive | gastroesophageal junction adenocarcinoma | predicted - sensitive | Afatinib | Phase II | Actionable | In a Phase II clinical trial, monotherapy with Gilotrif (afatinib) resulted in a moderate clinical benefit in ERBB2 (HER2)-positive patients with either gastroesophageal junction adenocarcinoma, metastatic esophageal cancer, or gastric adenocarcinoma, demonstrating a tumor reduction in 25% (5/20) according to RECIST, an objective partial response in 10% (2/20), a median progression-free survival of 2 months, and a median overall survival of 7 months (PMID: 30463996; NCT01522768). | 30463996 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Tucatinib | Phase I | Actionable | In a Phase I trial, treatment with Tukysa (tucatinib) resulted in a response rate of 14% (3/22; all partial responses (PR)) and a clinical benefit rate (PR plus stable disease for greater than or equal to 24 weeks) of 27% (6/22) in Erbb2 (Her2)-positive breast cancer patients (PMID: 28053022). | 28053022 |
| ERBB2 positive | colorectal cancer | predicted - sensitive | Timigutuzumab | Case Reports/Case Series | Actionable | In a Phase I trial, Timigutuzumab treatment resulted in a partial response in an ERBB2 (HER2)-positive colorectal cancer patient with a 56% reduction in tumor size following 56 days of treatment (PMID: 30018811; NCT01409343). | 30018811 |
| ERBB2 positive | breast cancer | predicted - sensitive | Trastuzumab Duocarmazine | Phase I | Actionable | In a Phase I trial, Trastuzumab Duocarmazine (SYD985) treatment resulted in an overall response of 33% (33/99) and a median progression-free survival of 9.4 months in patients with ERBB2 (HER2)-positive (50) or ERBB2 (HER2)-low (49) metastatic breast cancer (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 1014-1014; NCT02277717). | detail... |
| ERBB2 positive | stomach cancer | predicted - sensitive | ZW25 | Phase I | Actionable | In a Phase I trial, ZW25 treatment resulted in stable disease in 20% (1/5) of patients with ERBB2 (HER2)-positive gastric or esophageal cancers (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #255P; NCT02892123). | detail... |
| ERBB2 positive | ovarian carcinoma | sensitive | Trastuzumab Duocarmazine | Preclinical - Cell culture | Actionable | In a preclinical study, Trastuzumab Duocarmazine (SYD985) decreased survival of a ERBB2 (HER2)-positive ovarian carcinoma cell line in culture (PMID: 25589493). | 25589493 |
| ERBB2 positive | gastric adenocarcinoma | predicted - sensitive | Afatinib + Trastuzumab | Phase II | Actionable | In a Phase II clinical trial, the combination therapy of Gilotrif (afatinib) and Herceptin (trastuzumab) in ERBB2 (HER2)-positive patients with either gastroesophageal junction adenocarcinoma, metastatic esophageal cancer, or gastric adenocarcinoma resulted in a partial response in 8% (1/12) and disease control for 4 months or more in 17% (2/12) (PMID: 30463996; NCT01522768). | 30463996 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Trodusquemine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Trodusquemine (MSI-1436) inhibited tumor growth and metastasis in a ERBB2 (HER2)-positive human breast cancer cell line xenograft model (PMID: 24845231). | 24845231 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Lapatinib + MK2206 | Phase I | Actionable | In a Phase I trial, Tykerb (lapatinib) and MK2206 combination treatment resulted in stable disease for more than 6 months in 40% (2/5) of patients with ERBB2 (HER2)-positive breast cancer (PMID: 27026198). | 27026198 |
| ERBB2 positive | colorectal cancer | predicted - sensitive | Trastuzumab deruxtecan | Phase I | Actionable | In a Phase I trial, treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) resulted in an objective response rate (ORR) of 5% (1/20) and median progression-free survival of 4.0 months in patients with Erbb2 (Her2)-expressing colorectal cancer, with an ORR of 11.1% (1/9) and confirmed disease control rate of 100% (9/9) in patients with Erbb2 (Her2) expression of IHC 3+ (PMID: 32213540; NCT02564900). | 32213540 |
| ERBB2 positive | breast cancer | sensitive | MI130004 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MI130004 inhibited proliferation of ERBB2 (HER2)-receptor positive breast cancer cells in culture, and led to decreased tumor volume and improved survival in cell line xenograft models (PMID: 29440297). | 29440297 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Poziotinib | Phase II | Actionable | In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in a median progression-free survival of 4.04 months, and a disease control rate of 75.49% (77/102; 20 partial responses) in heavily-treated Erbb2 (Her2)-positive breast cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 237O; NCT02418689). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | CT-P6 | Phase III | Actionable | In a Phase III trial, CT-P6 demonstrated equivalence to reference Herceptin (trastuzumab) in patients with ERBB2 (HER2)-positive breast cancer, with 46.8% (116/248) of patients treated with CT-P6 achieving pathologic complete response compared to 50.4% (129/256) with Herceptin (trastuzumab) treatment (PMID: 28592386). | 28592386 |
| ERBB2 positive | sarcoma | predicted - sensitive | HER2 CAR-T cells | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with ERBB2 (HER2)-specific CAR-T cells resulted in stable disease for 12 weeks to 14 months in 4/17 evaluable patients with ERBB2 (HER2)-positive sarcomas and a median overall survival of 10.3 months (PMID: 25800760; NCT00902044). | 25800760 |
| ERBB2 positive | esophageal cancer | predicted - sensitive | ZW25 | Phase I | Actionable | In a Phase I trial, ZW25 treatment resulted in stable disease in 20% (1/5) of patients with ERBB2 (HER2)-positive gastric or esophageal cancers (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #255P; NCT02892123). | detail... |
| ERBB2 positive | ductal carcinoma in situ | predicted - sensitive | HER2-pulsed DC1 vaccine | Phase Ib/II | Actionable | In a Phase I/Ib clinical trial, vaccination with a HER2-peptide pulsed dendritic cell vaccine was well-tolerated and resulted in immune response in patients with ERBB2 (HER2)-positive ductal carcinoma in situ (DCIS), and resulted in pathologic complete response rate of 28% (12/42), compared to 8.3% (1/12) in patients with invasive breast cancer (PMID: 27965306). | 27965306 |
| ERBB2 positive | Her2-receptor positive breast cancer | predicted - sensitive | Ibrutinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Imbruvica (ibrutinib) inhibited Her family receptor signaling, resulted in apoptosis and growth inhibition in ERBB2 (HER2)-positive breast cancer cell lines in culture and in cell line xenograft models (PMID: 27256378). | 27256378 |
| ERBB2 positive | colorectal cancer | predicted - sensitive | Margetuximab-cmkb + MGD013 | Case Reports/Case Series | Actionable | In a Phase I trial, MGD013 and Margenza (margetuximab-cmkb) combination treatment resulted in a partial response in a patient with ERBB2 (HER2)-positive colorectal cancer (J Clin Oncol 38: 2020 (suppl; abstr 3004); NCT03219268). | detail... |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Varlitinib | Phase I | Actionable | In a Phase I expansion trial, 36% (5/14) of metastatic breast cancer patients positive for ERBB2 (HER2) demonstrated stable disease for up to 16 weeks when treated with Varlitinib (ARRY-334543) (Cancer Res May 1, 2009 69; 3603). | detail... |
| ERBB2 positive | gastric adenocarcinoma | no benefit | Ado-trastuzumab emtansine | Phase III | Actionable | In a Phase III trial (GATSBY), Kadcyla (trastuzumab emtansine) did not demonstrate efficacy benefit over Taxol (paclitaxel) in median overall survival (7.9 vs 8.6 months) in patients with previously treated ERBB2 (HER2)-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (PMID: 28343975; NCT01641939). | detail... 28343975 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | MYL-1401O + Paclitaxel | Phase III | Actionable | In a Phase III trial, MYL-1401O demonstrated safety and efficacy comparable to Herceptin (trastuzumab) when given in combination with Taxol (paclitaxel), resulted in an objective response rate of 69.6% in ERBB2 (HER2)-positive breast cancer patients (J Clin Oncol 34, 2016 (suppl; abstr LBA503)). | detail... |
| ERBB2 positive | breast cancer | sensitive | ADCT-502 | Preclinical - Pdx | Actionable | In a preclinical study, ADCT-502 demonstrated anti-tumor activity in ERBB2 (HER2)-expressing breast cancer cell line and patient-derived xenograft (PDX) models, including PDX models expressing low levels of ERBB2 (HER2) (Eur J Cancer, 2016, Vol. 69, Supp1, S28). | detail... |
| ERBB2 positive | stomach cancer | sensitive | HER2 Vaccine | Preclinical - Patient cell culture | Actionable | In a preclinical study, ERBB2 (HER2)-specific cytotoxic T-cell lines generated from gastric cancer patients demonstrated activity against autologous ERBB2 (HER2)-expressing gastric cancer cells in culture (PMID: 9754653). | 9754653 |
| ERBB2 positive | stomach cancer | predicted - sensitive | CAT-01-106 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with CAT-01-106 led to tumor growth inhibition and improved survival in ERBB2 (HER2)-positive gastric cancer cell line xenograft models (PMID: 32651200). | 32651200 |
| ERBB2 positive | Her2-receptor positive breast cancer | sensitive | Copanlisib | Preclinical | Actionable | In a preclinical study, breast cancer cell lines with a PIK3CA activating mutation and/or ERBB2 (HER2)-over expression demonstrated increased sensitivity to inhibition of proliferation by Aliqopa (copanlisib) in culture, compared to ERBB2 (HER2)-negative and wild-type PIK3CA cell lines (PMID: 24170767). | 24170767 |
| ERBB2 positive | stomach cancer | sensitive | Lapatinib + Paclitaxel | Phase III | Actionable | In a Phase III trial, second-line treatment using Tykerb (lapatinib) with paclitaxel demonstrated some efficacy in patients with HER2-positive advanced gastric cancer (PMID: 24868024). | 24868024 |
| ERBB2 pos PIK3CA act mut | uterine cancer | sensitive | Taselisib | Preclinical | Actionable | In a preclinical study, Taselisib (GDC-0032) inhibited growth of HER2 positive uterine cancer cell lines with PIK3CA mutations (PMID: 25172762). | 25172762 |
| ERBB2 pos PIK3CA act mut | Her2-receptor positive breast cancer | decreased response | Trastuzumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, ERBB2 (HER2)-positive breast cancer patients with PI3K pathway activation due to PTEN loss and/or PIK3CA activating mutation demonstrated a decreased median progression-free survival of 4.5 months, compared to 9.0 months for patients without PI3K pathway activation following treatment with a Herceptin (trastuzumab) containing regimen (PMID: 21676217). | 21676217 |
| ERBB2 pos PIK3CA act mut | Her2-receptor positive breast cancer | decreased response | Trastuzumab | Clinical Study - Cohort | Actionable | In a clinical study, ERBB2 (HER2)-positive breast cancer patients with PI3K pathway activation resulting from low PTEN expression and/or PIK3CA activating mutations demonstrated decreased progression-free survival following treatment with Herceptin (trastuzumab) compared to patients without PI3K pathway activation (PMID: 17936563). | 17936563 |
| ERBB2 pos PIK3CA act mut | Her2-receptor positive breast cancer | sensitive | Palbociclib + Pictilisib | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) and Pictilisib (GDC-0941) worked synergistically to inhibit survival of ERBB2 (HER2)-positive breast cancer cell lines harboring PIK3CA mutations in culture (PMID: 27020857). | 27020857 |
| ERBB2 pos PIK3CA act mut | Her2-receptor positive breast cancer | predicted - sensitive | Buparlisib + Trastuzumab | Phase I | Actionable | In a Phase I trial, the combination of Buparlisib (BKM120) and Herceptin (trastuzumab) was well tolerated and resulted in some preliminary efficacy in patients with ERBB2 (HER2)-positive breast cancer harboring PIK3CA activating mutations and/or PTEN mutations that had progressed on trastuzumab-based therapy (PMID: 24470511). | 24470511 |
| ERBB2 pos PIK3CA E545K | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of Herceptin (trastuzumab)-resistant ERBB2 (HER2) positive breast cancer cells harboring PIK3CA E545K in culture, and induced tumor regression in cell line xenograft models (PMID: 26920887). | 26920887 |
| ERBB2 pos PIK3CA E545K | Her2-receptor positive breast cancer | predicted - sensitive | Neratinib | Phase III | Actionable | In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). | 30867034 |
| ERBB2 pos PIK3CA mut | Her2-receptor positive breast cancer | decreased response | Lapatinib + Trastuzumab | Phase II | Actionable | In a Phase II trial, ERBB2-positive breast cancer patients harboring PIK3CA mutations demonstrated lower pathologic complete remission rate (12.5%) compared to those with wild-type PIK3CA (48.4%) after Herceptin (trastuzumab) and Tykerb (lapatinib) combination therapy (PMID: 26245675). | 26245675 |
| ERBB2 pos PIK3CA mut | Her2-receptor positive breast cancer | decreased response | Lapatinib + Trastuzumab | Clinical Study - Cohort | Actionable | In a clinical study, a retrospective analysis of the combined treatment, Herceptin (trastuzumab) and Tykerb (lapatinib), in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA (PMID: 28177460). | 28177460 |
| ERBB2 pos PIK3CA mut | Her2-receptor positive breast cancer | decreased response | Lapatinib | Clinical Study - Cohort | Actionable | In a clinical study, a retrospective analysis of Tykerb (lapatinib) treatment in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA (PMID: 28177460). | 28177460 |
| ERBB2 pos PIK3CA mut | Her2-receptor positive breast cancer | sensitive | AT13148 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AT13148 inhibited tumor growth in a ERBB2 (HER2)-positive human breast cancer cell line xenograft model harboring mutant PIK3CA (PMID: 22781553). | 22781553 |
| ERBB2 pos PIK3CA mut | Her2-receptor positive breast cancer | predicted - sensitive | Neratinib | Phase III | Actionable | In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). | 30867034 |
| ERBB2 pos PIK3CA mut | Her2-receptor positive breast cancer | decreased response | Capecitabine + Lapatinib | Phase III | Actionable | In a Phase III trial, Tykerb (lapatinib) and Xeloda (capecitabine) combination treatment resulted in decreased median progression free survival (4.3 vs. 6.4 months), median overall survival (17.3 vs. 27.8 months), and overall response rate(17.1% vs. 39.7%) in ERBB2 (HER2) positive breast cancer patients harboring PIK3CA mutations compared to PIK3CA wild type patients (PMID: 26920887). | 26920887 |
| ERBB2 pos PIK3CA mut | Her2-receptor positive breast cancer | decreased response | Trastuzumab | Clinical Study - Cohort | Actionable | In a clinical study, a retrospective analysis of Herceptin (trastuzumab) treatment in ERBB2 (HER2) positive breast cancer patients demonstrated patients harboring a PIK3CA mutation trended towards a decreased response when compared to patients with wild-type PIK3CA (PMID: 28177460). | 28177460 |
| ERBB2 pos PIK3CA K111N | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA K111N in culture, and induced tumor regression in cell line xenograft models (PMID: 26920887). | 26920887 |
| ERBB2 pos PIK3CA I391M | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell culture | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA K111N in culture (PMID: 26920887). | 26920887 |
| ERBB2 pos PIK3CA C420R | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell culture | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of ERBB2 (HER2) positive breast cancer cells harboring PIK3CA C420R in culture (PMID: 26920887). | 26920887 |
| ERBB2 pos PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited survival of Herceptin (trastuzumab)-resistant ERBB2 (HER2) positive breast cancer cells harboring PIK3CA H1047R in culture, and induced tumor regression in cell line xenograft models (PMID: 26920887). | 26920887 |
| ERBB2 pos PIK3CA H1047R | Her2-receptor positive breast cancer | predicted - sensitive | Neratinib | Phase III | Actionable | In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). | 30867034 |
| ERBB2 neg ERBB2 pos | Her2-receptor negative breast cancer | sensitive | LY411575 + Paclitaxel | Preclinical | Actionable | In a preclinical study, circulating tumor cells (CTC) from patients with ERBB2 (HER2)-negative breast cancer were demonstrated to contain both ERBB2 (HER2)-positive and ERBB2 (HER2)-negative subpopulations, and the combination of LY411575 and Taxol (paclitaxel) resulted in increased tumor growth inhibition in CTC-derived xenograft models compared to either agent alone (PMID: 27556950). | 27556950 |
| ERBB2 neg ERBB2 pos | Her2-receptor negative breast cancer | sensitive | Paclitaxel + RO4929097 | Preclinical | Actionable | In a preclinical study, circulating tumor cells (CTC) from patients with ERBB2 (HER2)-negative breast cancer were demonstrated to contain both ERBB2 (HER2)-positive and ERBB2 (HER2)-negative subpopulations, and the combination of RO4929097 and Taxol (paclitaxel) resulted in increased tumor growth inhibition in CTC-derived xenograft models compared to either agent alone (PMID: 27556950). | 27556950 |
| ERBB2 pos PIK3CA amp | Her2-receptor positive breast cancer | predicted - sensitive | Neratinib | Phase III | Actionable | In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). | 30867034 |
| ERBB2 pos PIK3CA E542K | Her2-receptor positive breast cancer | predicted - sensitive | Neratinib | Phase III | Actionable | In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). | 30867034 |
| ERBB2 pos PIK3CA E545D | Her2-receptor positive breast cancer | predicted - sensitive | Neratinib | Phase III | Actionable | In a Phase III trial (ExteNET), Nerlynx (neratinib) treatment resulted in improved 5-year invasive disease-free survival (92.4% vs 84.5%, HR=0.41, p=0.028) and clinical benefit (HR=0.40, p=0.041) compared to placebo in patients with ERBB2 (HER2)-positive early breast cancer who completed trastuzumab-based adjuvant therapy, and harbored PIK3CA amplification (n=61) or mutations (n=210), including H1047R (n=110), E542K (n=18), and E545K/D (n=82) (PMID: 30867034; NCT00878709). | 30867034 |