Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors

Launched by NOVARTIS PHARMACEUTICALS · May 27, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called [225Ac]Ac-ETN029 for patients with advanced cancers that express a protein known as DLL3. These cancers include small cell lung carcinoma, large cell neuroendocrine carcinoma of the lung, neuroendocrine prostate cancer, and gastroenteropancreatic neuroendocrine carcinoma. The main goals of the study are to find out if this treatment is safe, how well it works, and how it can be measured with imaging tests. The trial is currently not recruiting participants.

To be eligible for this trial, patients need to be at least 18 years old and have a specific type of cancer that has not responded to at least one previous treatment, particularly those containing platinum. Participants will undergo tests to ensure they are suitable for the study, and they can expect to receive the new treatment along with monitoring for side effects and effectiveness. It’s important to note that certain health conditions may exclude someone from joining the trial, so a healthcare provider will review each patient's medical history to determine eligibility.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age ≥ 18 years old
• * Patients with one of the following indications:
• • Locally advanced, unresectable, or metastatic SCLC with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy, unless patient was ineligible to receive such therapy. Prior DLL3-targeted therapy is allowed. For dose expansion, patients should have received no more than 2 prior lines of systemic therapy.
• • Dose escalation only: LCNEC of the lung with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy, unless patient was ineligible to receive such therapy.
• • Dose expansion only: Locally advanced, unresectable, or metastatic de novo or castration-resistant, treatment-emergent NEPC with neuroendocrine differentiation confirmed by local histology and NEPC marker expression (e.g., chromogranin, synaptophysin) confirmed by local IHC. Prior PSMA-targeted, Lu-177-based RLT is allowed. Patients must have at least one measurable lesion (per RECIST 1.1) that shows 111In-ETN029 uptake higher than surrounding tissues on SPECT/CT as assessed by the Investigator.
• • Dose expansion only: Locally advanced, unresectable, or metastatic GEP-NEC with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy, unless patient was ineligible to receive such therapy. Patients must have at least one measurable lesion (per RECIST 1.1) that shows 111In-ETN029 uptake higher than surrounding tissues on SPECT/CT as assessed by the Investigator.
• Exclusion Criteria:
• • Absolute neutrophil count (ANC) \< 1.0 x 109/L, hemoglobin \< 9 g/dL, or platelet count \< 75 x 109/L
• • QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec
• • eGFR \< 60 mL/min (\<0.835 mL/s), calculated using the CKD-EPI 2021 formula or measured
• • Unmanageable urinary tract obstruction or urinary incontinence
• • Presence of leptomeningeal disease, of symptomatic CNS metastases or of CNS metastases that require local CNS-directed therapy
• • History of or current interstitial lung disease or pneumonitis ≥ Grade 2
• • Any prior DLL3-targeted therapy (except for SCLC) and any prior RLT (except for NEPC)
• • Other protocol-defined inclusion/exclusion criteria may apply.