A Phase 1, Multicenter Imaging Study of LNTH-2403 in Participants With Locally Advanced or Metastatic Solid Tumors.

NCT07272642 | Not Yet Recruiting Phase 1

• 1 other identifier: DUNP19-AU-101
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

LNTH-2403 (177Lu-DOTA-DUNP19) is a lutetium-177 radiolabeled, fully humanized monoclonal antibody (mAb) that binds with high specificity and affinity to leucine-rich repeat containing 15 (LRRC15), a transforming growth factor (TGF) - β-driven biomarker expressed on the cell membrane of cancer cells and/or cancer-associated fibroblasts 9CAFs) in select tumor types. Upon binding, LNTH-2403 is rapidly internalized, such that it can serve as a dual-purpose agent for both non-invasive imaging and radiotheranostic treatment of LRRC15- positive tumors. This first-in-human (FIH) imaging study will evaluate the safety and imaging of LNTH-2403 in participants with locally advanced or metastatic solid tumors.

Conditions

Imaging; Colorectal Cancer; Head and Neck Squamous Cell Carcinoma; Non-Small Cell Lung Cancer; Triple Negative Breast Cancer (TNBC)

Keywords

imaging; colorectal cancer; Head and Neck squamous cell carcinoma,; non-small cell lung cancer,; triple negative breast cancer

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability of a single dose of LNTH-2403

  Frequency and severity of adverse events (AE)s and serious adverse events (SAEs)using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  90 days

Secondary Outcomes (1)

• To assess the biodistribution of LNTH-2403 in selected organs and tumor lesions.

  90 days

Other Outcomes (2)

• Exploratory: • To explore agreement between LNTH-2403 imaging and LRRC15 and FAP expression by IHC analysis

  90 days

• Exploratory: To assess the sensitivity, specificity, and accuracy of LNTH-2403 for imaging

  90 days

Study Arms (1)

Single-arm, Single dose, open-label study

EXPERIMENTAL

LNTH-2403 at a dose of 20 mCi(0.74 GBq)

Drug: LNTH-2403

Interventions

LNTH-2403 DRUG

LNTH-2403 (177Lu-DOTA-DUNP19) is a lutetium-177 radiolabeled, fully humanized monoclonal antibody (mAb)

Single-arm, Single dose, open-label study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give written informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
• Participant is ≥ 18 years of age at the time of signing the informed consent.
• Participant has a documented history of incurable, histopathologically confirmed CRC, HNSCC,NSCLC (squamous or non-squamous histology) or TNBC with either locally advanced disease which has progressed despite (or is ineligible for) available radical standard of care treatments and has subsequently exhausted available standard of care palliative intent systemic therapies or established metastatic disease where available standard of care systemic therapies have been exhausted.
• Has had a SOC CT or MRI scan within 8 weeks prior to signing informed consent that indicates the presence of at least 1 site of new or residual disease. SOC baseline images must be available for submission to the centralized imaging reader as reference
• Participant must provide an archived tumor tissue sample.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Participant has at least 1 visceral lesion that has not been treated with external beam radiation therapy (EBRT).
• Participants of childbearing potential (CBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. Participants of CBP are defined as those who are not surgically sterile or post-menopausal. Participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Participants \< 50 years of age who meet the criteria for postmenopausal status without previous surgical sterilization should be considered for further investigation with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels to confirm serological post-menopausal status.
• Participants of CBP must agree to use a highly effective method of contraception during the study and for 3 months after the injection of LNTH-2403.
• Male participants who are able to father a child must agree to avoid impregnating a partner and to adhere to a highly effective method of contraception during the study and for 3 months after the injection of LNTH-2403. All male participants must agree to not donate sperm during the study and for 3 months after the injection of LNTH-2403.

You may not qualify if:

• Has any medical condition that would, in the Investigator's judgment, prevent the participant's full participation in the clinical study due to safety concerns or compliance with clinical study procedures.
• Has a history of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics, LNTH-2403, or any of its excipients.
• Has inadequate organ functions as reflected in laboratory parameters:
• Estimated glomerular filtration rate (eGFR) (calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation) ≤ 50 mL/min/1.73m2
• Platelet count \<100 x 10\^9 /L
• Hemoglobin \< 9 g/dL
• Absolute neutrophil count \< 1.0 × 109/L
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x upper limit of normal (ULN), or ≥ 5 x ULN for participants with known liver metastases
• Total bilirubin ≥ 1.5 x ULN, except for participants with documented Gilbert's syndrome who are eligible if total bilirubin is ≤ 3 x ULN
• For participants not taking warfarin or other anticoagulants: international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤ 1.5 × ULN. Participants taking warfarin must be on a stable dose that results in a stable INR \< 3.5. Among participants receiving other anticoagulant therapy, PT or aPTT must be within the intended therapeutic range of the anticoagulant.
• Has clinically significant cardiovascular/ cerebrovascular disease defined as cerebral vascular accident, stroke, carotid artery disease transient ischemic attack (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class \>II) or serious cardiac arrhythmia.
• Has a marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval calculated with Fredericia's correction (QTcF) \> 470 msec for females and QTcF \> 450 msec for males);
• Has a history of or has additional risk factors for torsade's de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Is participating in an interventional trial or has received an investigational anticancer agent within 5 half-lives of the time of informed consent signature or is expected to enroll in an interventional trial on or before the imaging timepoint during Days 3-5.
• Has been treated with an LRRC15-targeted investigational product.

Sponsors & Collaborators

• Radiopharm Theranostics, Ltd: lead

Study Sites (1)

Icon Cancer Centre Hollywood

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Dimitris Voliotis, MD

CONTACT

+1 646 535 5017 5017; dv@radiopharmtheranostics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2025
• First Posted: December 9, 2025
• Study Start: January 30, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)