Patritumab Deruxtecan (HER3-DXd / U3-1402) Clinical Trials (May 2026): 23 Recruiting — First HER3 ADC in Phase 3
Last updated: May 26, 2026
🗓️ At ASCO 2026 (May 29 – June 2, Chicago): Updated data from HERTHENA-Breast03 (NCT07060807, MK-1022-016 — the registrational Phase 3 in breast cancer) and from the broader HER3-DXd program in solid tumors (combination with pembrolizumab, GI basket, NRG1 fusion cohort) are widely anticipated. Patritumab deruxtecan is the first HER3-directed ADC to reach Phase 3 in oncology, and the ASCO 2026 readouts will inform both the registrational pathway and the indication-expansion strategy.
About Patritumab Deruxtecan
Drug profile:
Patritumab deruxtecan (HER3-DXd; development code U3-1402; Merck code MK-1022) is an investigational antibody-drug conjugate developed by Daiichi Sankyo in partnership with Merck (worldwide co-development announced 2022). It is the first HER3-targeted ADC to reach Phase 3 in oncology.
Mechanism of action:
HER3-DXd combines patritumab — a fully human anti-HER3 (ERBB3) monoclonal antibody — with deruxtecan, a potent topoisomerase I inhibitor payload (an exatecan derivative), via a tumor-selective cleavable tetrapeptide linker. The drug-to-antibody ratio is approximately 8 (the same DXd platform used in trastuzumab deruxtecan / T-DXd). After binding HER3-expressing tumor cells, HER3-DXd is internalized and releases the deruxtecan payload intracellularly, producing direct DNA damage. The payload is membrane-permeable, which creates a "bystander effect" — neighboring tumor cells are also killed even if they don't express HER3 themselves. HER3 (also called ErbB3) is broadly overexpressed across many cancer types — breast, lung (especially EGFR-mutant NSCLC after EGFR-TKI resistance), gastrointestinal, head and neck, and others — making it a broad oncology target.
Regulatory status:
- FDA approvals: none yet. Patritumab deruxtecan is investigational.
- FDA designations: Breakthrough Therapy Designation in EGFR-mutant non-small cell lung cancer after EGFR-TKI and platinum-based chemotherapy progression (granted 2021 based on HERTHENA-Lung01 data).
- Phase 3 status: 1 Phase 3 trial currently recruiting (HERTHENA-Breast03, NCT07060807) — see Recruiting Trials below. The HERTHENA-Lung02 Phase 3 in EGFR-mutant NSCLC has reported topline results; FDA submission was anticipated.
- Anticipated first approval: based on the HERTHENA-Breast03 or HERTHENA-Lung02 Phase 3 readouts, expected 2026-2027.
Active Research Directions in 2026
- HERTHENA-Breast03 — the registrational breast cancer Phase 3 (NCT07060807, MK-1022-016): HER3-DXd in advanced breast cancer that has progressed on prior therapies — the lead registration path for the first FDA approval.
- EGFR-mutant NSCLC post-EGFR-TKI — HER3 is upregulated in EGFR-resistant NSCLC, making HER3-DXd a mechanism-rational post-osimertinib option. The HERTHENA-Lung01 Phase 2 data established proof of concept; the HERTHENA-Lung02 Phase 3 confirmatory study has reported topline results.
- NRG1 fusion-positive solid tumors (NCT06383884) — a unique mechanism: NRG1 (neuregulin-1) is the natural HER3 ligand, so NRG1 fusions drive HER3 signaling directly. HER3-DXd is one of the few therapies designed for this rare-but-actionable fusion class (which occurs in some pancreatic, NSCLC, breast, and other cancers).
- Combination with pembrolizumab (NCT06797635) — HER3-DXd + pembrolizumab + other anticancer agents in solid tumors. Tests the hypothesis that HER3-targeted ADC payload delivery sensitizes tumors to checkpoint immunotherapy.
- Gastrointestinal cancer expansion (NCT06596694 MK-1022-011) — patritumab deruxtecan in advanced/metastatic GI cancers, expanding the indication footprint beyond breast and lung.
- HER2-positive solid tumor combinations (NCT06686394) — HER3-DXd with other anticancer agents in HER2-positive disease (cross-receptor combination strategies in the ErbB family).
- Pediatric expansion (NCT06941272) — patritumab deruxtecan in pediatric relapsed/refractory solid tumors. Notable for being one of the few HER3-targeted programs reaching pediatric oncology.
- HER3 PET/CT companion imaging (NCT06222489) — whole-body HER3 quantification with radiolabelled patritumab deruxtecan PET/CT. Could enable HER3-expression-based patient selection (a missing piece given that HER3 IHC scoring is not yet standardized like HER2 IHC).
- Cross-platform appearances — HER3-DXd is also a treatment arm in the I-SPY 2 neoadjuvant breast cancer platform trial (NCT01042379), one of multiple Substudy 06D combinations in gastroesophageal cancer (NCT06445972), and Substudy 06C with pembrolizumab + chemotherapy combinations (NCT06469944).
Recruiting Trials by Indication
Breast Cancer — Lead Indication (Phase 3 + foundational Phase 2)
- NCT07060807 — HERTHENA-Breast03 (Phase 3, MK-1022-016): patritumab deruxtecan in advanced breast cancer that has progressed on prior therapies. The registrational Phase 3 — basis for the first anticipated FDA approval.
- NCT04965766 — Patritumab Deruxtecan (U3-1402) in unresectable locally advanced or metastatic HER3-expressing breast cancer (Phase 2 foundational study)
- NCT01042379 — I-SPY 2: Patritumab deruxtecan is a treatment arm in this long-running neoadjuvant adaptive platform trial in breast cancer.
NRG1 Fusion-Positive Solid Tumors (unique mechanism)
NRG1 (neuregulin-1) is the natural HER3 ligand. NRG1 fusions drive HER3 signaling directly, making HER3-targeted therapy particularly mechanistically relevant. NRG1 fusions occur in some pancreatic, lung, breast, and other cancers (rare but actionable):
- NCT06383884 — Patritumab Deruxtecan in patients with solid tumors harboring an NRG1 fusion (Phase 2)
Combinations with Pembrolizumab (KEYNOTE / MK-1022 program)
- NCT06797635 — Patritumab Deruxtecan + Pembrolizumab with other anticancer agents in solid tumors
- NCT06731907 — Pembrolizumab ± chemotherapy + additional treatments (including HER3-DXd arms)
- NCT04165070 — KEYMAKER-U01 Substudy 01A: Pembrolizumab combinations including HER3-DXd
- NCT06469944 — Substudy 06C: Investigational agents (incl. HER3-DXd) with pembrolizumab and chemotherapy
- NCT06445972 — Substudy 06D: Combination therapies in 2L gastroesophageal adenocarcinoma (MK-1022 arm)
Gastrointestinal Cancers
- NCT06596694 — Patritumab Deruxtecan in gastrointestinal cancers (MK-1022-011)
HER2-Positive Solid Tumors (cross-receptor combinations)
- NCT06686394 — Patritumab Deruxtecan with other anticancer agents in HER2-positive solid tumors
Broad Solid Tumor / Basket Studies
- NCT06172478 — HER3-DXd in subjects with locally advanced or metastatic solid tumors (Phase 2 basket)
- NCT06298084 — Dose-Expansion Modular Study (safety, tolerability, anti-tumor activity)
Pediatric (Relapsed / Refractory Solid Tumors)
- NCT06941272 — Patritumab Deruxtecan in pediatric participants with relapsed or refractory solid tumors
HER3 PET/CT Imaging Companion
- NCT06222489 — Whole-body HER3 quantification with radiolabelled patritumab deruxtecan PET/CT — could enable HER3-expression-based patient selection
Showing the 23 currently-recruiting patritumab deruxtecan / HER3-DXd trials in the ClinTrialFinder corpus. View the latest patritumab deruxtecan search on ClinicalTrials.gov. Note: HERTHENA-Lung02 (NCT04619916) — the EGFR-mutant NSCLC Phase 3 — has completed enrollment and is not currently recruiting; topline results have been reported.
Patient Selection and HER3 Biomarker Testing
Patient selection for HER3-DXd is less standardized than for T-DXd (HER2 IHC). Key considerations:
- HER3 (ERBB3) expression by IHC — many trials enroll based on HER3 immunohistochemistry, but the optimal cutoff is still being defined. Patients with HER3-low tumors may still benefit because of the deruxtecan bystander effect.
- NRG1 fusion — detected on tumor next-generation sequencing or RNA-seq. NRG1 fusions are the most mechanistically clear-cut indication for HER3-DXd (NRG1 is the HER3 ligand; fusion drives HER3 signaling).
- EGFR mutation status (NSCLC) — EGFR-mutant NSCLC after EGFR-TKI (osimertinib) progression is the established setting. HER3 upregulation is a known EGFR-TKI resistance mechanism, making HER3-DXd mechanism-rational.
- HER3 PET/CT imaging (NCT06222489) — investigational imaging-based patient selection. Currently a research tool; could become a companion diagnostic if the HERTHENA-Lung02 or HERTHENA-Breast03 readouts support PET-based selection.
- Prior treatment history — most trials enroll patients who have progressed on prior standard therapies for their cancer type. Specific prior-therapy requirements vary by trial.
- Comprehensive genomic profiling (e.g., Foundation Medicine, Tempus, Guardant360) — recommended to identify NRG1 fusions and to characterize the broader molecular context. Knowing your EGFR / HER2 / NRG1 status helps determine which HER3-DXd trial may best apply.
Side Effects and Practical Considerations
- ⚠️ Interstitial lung disease (ILD) / pneumonitis — the most important class-level safety concern for all deruxtecan-based ADCs (including T-DXd). Rare but potentially serious lung inflammation. Any new respiratory symptoms (cough, shortness of breath, fever) require immediate evaluation, treatment interruption, and (if confirmed) corticosteroid management. Patients with prior ILD, active pneumonia, or significant pulmonary impairment require careful pre-treatment evaluation.
- Nausea and vomiting — very common; standard practice is prophylactic antiemetic regimens.
- Fatigue — common throughout treatment.
- Alopecia — hair loss is common.
- Low blood counts — neutropenia, anemia, thrombocytopenia. Routine CBC monitoring; dose modifications per protocol if Grade 3+.
- Liver enzyme elevations — observed in some patients; routine LFT monitoring required.
- Decreased appetite and constipation — common; managed supportively.
- Combination-specific toxicities — HER3-DXd + pembrolizumab adds immune-related event risk. Combinations with chemotherapy add the toxicities of the partner regimen.
Frequently Asked Questions
What is patritumab deruxtecan (HER3-DXd)?
Patritumab deruxtecan (HER3-DXd; development code U3-1402; Merck code MK-1022) is an investigational antibody-drug conjugate developed by Daiichi Sankyo in partnership with Merck. It is the first HER3-targeted ADC to reach Phase 3 in oncology. Patritumab is a fully human anti-HER3 (ERBB3) monoclonal antibody; deruxtecan is the topoisomerase I inhibitor payload (the same DXd platform used in T-DXd / Enhertu). HER3 is broadly overexpressed across breast, lung (especially EGFR-mutant NSCLC after EGFR-TKI resistance), GI, and other cancers. No FDA approvals yet; HERTHENA-Breast03 (NCT07060807) is the registrational Phase 3.
What cancers is patritumab deruxtecan being tested in?
Breast cancer (lead indication: HERTHENA-Breast03 NCT07060807 Phase 3; NCT04965766 Phase 2 in HER3-expressing breast; I-SPY 2 neoadjuvant arm NCT01042379), EGFR-mutant NSCLC after EGFR-TKI failure (HERTHENA-Lung01 Phase 2 + HERTHENA-Lung02 Phase 3 — Lung02 has reported topline), GI cancers (NCT06596694 MK-1022-011), HER2+ solid tumors (NCT06686394), NRG1 fusion-positive tumors (NCT06383884 — unique mechanism), combination with pembrolizumab (NCT06797635), pediatric R/R solid tumors (NCT06941272), and HER3 PET/CT imaging companion (NCT06222489).
How does HER3-DXd differ from T-DXd?
Both are deruxtecan-based ADCs from Daiichi Sankyo's DXd platform — same exatecan-derivative payload, same cleavable linker, same drug-to-antibody ratio (~8). The difference is the antibody backbone and its target: T-DXd uses an anti-HER2 antibody; HER3-DXd uses an anti-HER3 (ERBB3) antibody. HER3 has a distinct expression pattern — broadly overexpressed across many cancer types and especially upregulated in EGFR-mutant NSCLC after EGFR-TKI resistance, making HER3-DXd a particularly relevant post-osimertinib option. Patient selection also differs: T-DXd uses HER2 IHC scoring; HER3-DXd selection is less standardized and a companion HER3 PET/CT imaging trial (NCT06222489) is recruiting.
What are the main side effects of patritumab deruxtecan?
The class-level safety concern for all deruxtecan-based ADCs is interstitial lung disease (ILD) / pneumonitis — rare but potentially serious; close monitoring and prompt treatment interruption at any pulmonary symptom. Common side effects include nausea (very common; prophylactic antiemetics standard), vomiting, fatigue, alopecia, low blood counts (neutropenia, anemia, thrombocytopenia), liver enzyme elevations, decreased appetite, and constipation. Combination-specific toxicities depend on the partner regimen.
Find Patritumab Deruxtecan and HER3 ADC Trials Matched to Your Situation
Use ClinTrialFinder's AI-powered matching to find patritumab deruxtecan (HER3-DXd), other HER3-directed therapies, and ADC trials based on your specific cancer type, HER3 expression status, NRG1 fusion status, EGFR / HER2 status, prior treatments, and biomarker context.
Find Matching Trials
This page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here.
