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| Ref Type | Journal Article | ||||||||||||
| PMID | (37801674) | ||||||||||||
| Authors | Krop IE, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Yamamoto Y, Alvarez RH, Toyama T, Takahashi M, Osaki A, Saji S, Sagara Y, O'Shaughnessy J, Ohwada S, Koyama K, Inoue T, Li L, Patel P, Mostillo J, Tanaka Y, Sternberg DW, Sellami D, Yonemori K | ||||||||||||
| Title | Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. | ||||||||||||
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| Abstract Text | Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study.Adults with disease progression on previous therapies were eligible. Patients in the dose-escalation, dose-finding, and dose-expansion parts received HER3-DXd 1.6-8.0 mg/kg intravenously once every 3 weeks or one of two alternative dosing regimens. In the dose-escalation part, the primary objectives were to determine the maximum tolerated dose and recommended dose for expansion (RDE). The safety and efficacy of the RDE were assessed during dose expansion.One hundred eighty-two enrolled patients received ≥1 dose of HER3-DXd. Patients had a median of five previous therapies for advanced disease. Efficacy results are reported across clinical subtypes: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer (n = 113; objective response rate [ORR], 30.1%; median progression-free survival [mPFS], 7.4 months), triple-negative breast cancer (n = 53; ORR, 22.6%; mPFS, 5.5 months), and HER2-positive breast cancer (n = 14; ORR, 42.9%; mPFS, 11.0 months). Objective responses were observed in cancers with HER3-high and HER3-low membrane expression. Dose-limiting toxicities observed during dose selection were decreased platelet count and elevated aminotransferases. In dose expansion, GI and hematologic toxicities were the most common treatment-emergent adverse events (TEAEs) observed. Grade ≥3 TEAEs were observed in 71.4% of patients, and 9.9% discontinued treatment because of TEAEs. Three grade 3 and one grade 5 treatment-related interstitial lung disease events occurred.HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes. These data warrant further evaluation of HER3-DXd in patients with HER3-expressing metastatic breast cancer. | ||||||||||||
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| ERBB3 positive | Her2-receptor negative breast cancer | predicted - sensitive | Patritumab deruxtecan | Phase Ib/II | Actionable | In a Phase I/II trial (U31402-A-J101), Patritumab deruxtecan (U3-1402) therapy demonstrated safety and efficacy in previously treated metastatic hormone receptor-positive, ERBB2 (HER2)-negative breast cancer patients expressing ERBB3 (HER3) (n=113), with an objective response rate of 30.1%, disease control rate of 80.5%, with partial response in 30.1% and stable disease in 50.4% of patients, median progression-free survival of 7.4 mo, and median overall survival of 14.6 mo (PMID: 37801674; NCT02980341). | 37801674 |
| ERBB3 over exp | Her2-receptor positive breast cancer | predicted - sensitive | Patritumab deruxtecan | Phase Ib/II | Actionable | In a Phase I/II trial (U31402-A-J101), Patritumab deruxtecan (U3-1402) therapy demonstrated safety and efficacy in previously treated metastatic ERBB2 (HER2)-positive breast cancer patients with high ERBB3 (HER3) (>/=75% membrane positivity) levels (n=14), with an objective response rate of 42.9%, disease control rate of 92.9%, with partial response in 42.9% and stable disease in 50% of patients, median progression-free survival of 11 mo, and median overall survival of 19.5 mo (PMID: 37801674; NCT02980341). | 37801674 |
| ERBB3 over exp | triple-receptor negative breast cancer | predicted - sensitive | Patritumab deruxtecan | Phase Ib/II | Actionable | In a Phase I/II trial (U31402-A-J101), Patritumab deruxtecan (U3-1402) therapy demonstrated safety and efficacy in previously treated metastatic triple-negative breast cancer patients with high ERBB3 (HER3) (>/=75% membrane positivity) levels (n=53), with an objective response rate of 22.6%, disease control rate of 79.2%, with partial response in 22.6% and stable disease in 56.6% of patients, median progression-free survival of 5.5 mo, and median overall survival of 14.6 mo (PMID: 37801674; NCT02980341). | 37801674 |