Investigational Drug
Patritumab deruxtecan
TrialFetch AI Analysis
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Overview
Patritumab deruxtecan (HER3-DXd; U3-1402) is an investigational antibody–drug conjugate studied in lung and breast cancers. Its clinical results include a randomized phase 3 lung-cancer trial, but the overall-survival data reported from that trial were not yet mature. (ascopubs.org)
Mechanism of action
The drug combines patritumab, an antibody targeting HER3, with deruxtecan, a topoisomerase I inhibitor. A cleavable linker connects the antibody to the drug payload, allowing the conjugate to deliver chemotherapy to HER3-expressing cells. (pmc.ncbi.nlm.nih.gov)
Efficacy
- EGFR-mutated non–small-cell lung cancer (NSCLC): In the single-arm phase 2 HERTHENA-Lung01 analysis, after prior EGFR-targeted therapy and platinum chemotherapy, 29.8% of 225 patients had a confirmed tumor response. Median response duration was 6.4 months and median progression-free survival was 5.5 months. (pmc.ncbi.nlm.nih.gov)
- Randomized lung-cancer comparison: In phase 3 HERTHENA-Lung02, involving 586 patients whose EGFR-mutated NSCLC had progressed after a third-generation EGFR inhibitor, response rates were 35.2% with patritumab deruxtecan and 25.3% with platinum-based chemotherapy. Median progression-free survival was 5.8 versus 5.4 months, respectively (hazard ratio 0.77). Overall-survival results were immature at the reported analysis. (ascopubs.org)
- Breast cancer: In the single-arm phase 2 ICARUS-BREAST01 study, 53.5% of 99 patients with previously treated hormone receptor–positive, HER2-negative metastatic breast cancer had a response. That result cannot establish how the drug compares with another treatment. (pubmed.ncbi.nlm.nih.gov)
Safety
In HERTHENA-Lung01, 12 of 225 patients (5.3%) had treatment-related interstitial lung disease, including one fatal case. In HERTHENA-Lung02, commonly reported treatment-emergent events included nausea, thrombocytopenia and fatigue; adverse events led to treatment discontinuation in 11% of patients receiving patritumab deruxtecan versus 10% receiving chemotherapy. In ICARUS-BREAST01, commonly reported treatment-related events included fatigue (83%) and nausea (75%). (pmc.ncbi.nlm.nih.gov)
Further reading
- HERTHENA-Lung01 phase 2 journal article
- HERTHENA-Lung02 phase 3 conference abstract
- ICARUS-BREAST01 phase 2 journal article
Last updated: Sep 2026
Active trials using Patritumab deruxtecan
Found 3 active trials using this drug:
TrialFetch AI summary: Adults with advanced or metastatic KRAS G12C-mutated nonsquamous NSCLC that has progressed after 1–2 prior lines including platinum chemotherapy and PD-1/PD-L1 therapy, and who have not received prior KRAS-targeted therapy, receive calderasib, a KRAS G12C inhibitor, combined with either patritumab deruxtecan (HER3-directed ADC), sacituzumab tirumotecan (TROP2-directed ADC), or cetuximab (EGFR-directed antibody).
ClinicalTrials.gov ID: NCT07286149
TrialFetch AI summary: Adults with HR-positive, HER2-negative unresectable locally advanced or metastatic breast cancer progressing after CDK4/6 inhibitor plus endocrine therapy, or recurring during or within 24 months of adjuvant CDK4/6 inhibitor therapy, are randomized to patritumab deruxtecan or physician’s choice of chemotherapy or trastuzumab deruxtecan. Patritumab deruxtecan is a HER3-targeted antibody–drug conjugate that delivers a topoisomerase I inhibitor payload.
ClinicalTrials.gov ID: NCT07060807
TrialFetch AI summary: Patients with HER2-positive unresectable locally advanced or metastatic breast cancer and ECOG performance status 0–1 receive patritumab deruxtecan with trastuzumab, trastuzumab plus pertuzumab, or trastuzumab plus tucatinib. Patritumab deruxtecan is an investigational HER3-directed antibody–drug conjugate carrying a topoisomerase I inhibitor; two arms require prior progression on trastuzumab deruxtecan.
ClinicalTrials.gov ID: NCT06686394
