Actively Recruiting
Patritumab Deruxtecan in Patients With Solid Tumor Harboring an NRG1 Fusion
Led by Samsung Medical Center · Updated on 2025-12-15
30
Participants Needed
1
Research Sites
245 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
The NRG1 gene is located on chromosome 8 (8p12 region) and encode NRG1. NRG1 gene is translated to generate six different proteins (I-VI) and at least 31 isoforms. NRG1 proteins are structurally related to EGF and contain an EGF-like motif that binds and activates ErbB3 and ErbB4. Upon ligand binding, these receptors form homodimers or heterodimers, which results in phosphorylation of the intrinsic kinase domain, and activation of the PI3K-AKT, MAPK, and other pathways. The overall incidence of NRG1 fusions is very rare. In many tumor types, only limited numbers of NRG1 fusion variant have been identified. By percentage, there is no organ dominance of the presence of NRG1 fusions. In an analysis of 21, 858 tumor specimens that underwent anchored multiplex PCR for targeted RNA sequencing, the prevalence of NRG1 fusions was 0.2%. Of these, CD74 was the most common partner (29%), followed by ATP1B1 (10%), SDC4 (7%), and RBPMS (5%), and most CD74-NRG1 fusions have been reported in patients with lung IMA. NRG1 fusions result in aberrant expression of the epidermal growth factor (EGF)-like domain of neuregulin-1 (NRG1) on the cell surface binds primarily to ErbB3 and ErbB4, leading to heterodimerization or oligomerization with other ERBB family members. NRG1-mediated activation of ErbB3 promotes dimerization with EGFR, ErbB2, and ErbB4. These partners phosphorylate ErbB3, forming docking sites for SH2-domain proteins, leading to pathologic activation of multiple signal transduction pathways, including the phosphoinositide 3-kinase (PI3K) pathway. Subsequently, ErbB3 expression was noted at high levels, and the proteins were phosphorylated, in fusion-positive cases. Targeting ErbB3 signaling therefore represents a promising therapeutic approach for patients with NRG1 fusion-positive malignancies.
CONDITIONS
Official Title
Patritumab Deruxtecan in Patients With Solid Tumor Harboring an NRG1 Fusion
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed informed consent before any study procedures
- Male or female aged 18 years or older (following local legal age of consent)
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor not suitable for curative surgery or radiation
- Documented presence of NRG1 fusion detected from tumor tissue or blood sample
- At least one measurable lesion confirmed by investigator per RECIST v1.1
- Willing and able to provide sufficient tumor tissue sample
- Eastern Cooperative Oncology Group performance status of 0 or 1 at screening
- Adequate bone marrow and organ function based on laboratory tests within 14 days before treatment start
- Platelet count of at least 100,000/mm3
- Hemoglobin level of at least 9.0 g/dL
- Absolute neutrophil count of at least 1,500/mm3
- Serum creatinine ≤1.5 times upper limit of normal or creatinine clearance ≥30 mL/min
- Liver enzymes (AST/ALT) ≤3 times upper limit of normal (≤5 if liver metastases present)
- Total bilirubin ≤1.5 times upper limit of normal if no liver metastases (≤3 if Gilbert's syndrome or liver metastases)
- Serum albumin level of at least 2.5 g/dL
- Coagulation tests within acceptable range, including if on anticoagulants
You will not qualify if you...
- History or current diagnosis of interstitial lung disease or suspected ILD on imaging
- Severe respiratory compromise from lung diseases like recent pulmonary embolism, severe asthma, COPD, restrictive lung disease, or pleural effusion
- Autoimmune or inflammatory disorders with lung involvement, or prior complete pneumonectomy
- Chronic use of systemic corticosteroids above 10 mg prednisone or equivalent or other immunosuppressive therapy prior to enrollment
- Evidence of leptomeningeal disease or active spinal cord compression or brain metastases
- Inadequate washout from prior therapies or treatments as defined by specific timeframes before Cycle 1 Day 1
- Prior treatment with anti-HER3 antibodies, single-agent topoisomerase I inhibitors, or antibody drug conjugates containing topoisomerase I inhibitors
- Unresolved toxicities from previous anticancer therapy above grade 1 except alopecia
- History of other active cancers within 3 years except certain adequately treated or low-risk cancers
- Uncontrolled or significant cardiovascular disease prior to treatment
- Active hepatitis B or C infection within 28 days before treatment start
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Samsung Medical Center
Seoul, South Korea, 06351
Actively Recruiting
Research Team
S
Se-Hoon Lee, MD, PhD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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