Skip to main content
Back to Trials
NCT07006727PHASE1Recruiting

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

Novartis Pharmaceuticals

Start Date

10/16/2025

Completion Date

8/29/2031

Summary

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[225Ac\]Ac-ETN029 and the safety and imaging properties of \[111In\]In-ETN029 in patients aged ≥ 18 years with locally advanced or metastatic DLL3 positive cancers.

Detailed Description

This is a phase I, open-label, multi-center study to evaluate the safety, tolerability, dosimetry, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of 225Ac-ETN029 in patients with advanced DLL3-expressing solid tumors. The study consists of a dose escalation part, followed by a dose expansion part. Once the recommended radioactive dose(s) of 225Ac-ETN029 for further clinical evaluation are determined, the dose expansion part will further characterize the safety, tolerability, and preliminary anti-tumor activity of 225Ac-ETN029. The study will also enable an initial evaluation of the safety, dosimetry, PK, and imaging properties of 111In-ETN029.

Eligibility Criteria

Age Range: 18 years to 100 years

Inclusion Criteria: * Age ≥ 18 years old * Patients with one of the following indications: Dose Escalation Only: * Locally advanced, unresectable, or metastatic SCLC with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy (prior DLL3-targeted therapy allowed). * LCNEC of the lung with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy. * Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) confirmed by local histopathology, for whom no standard therapy is available, tolerated, or appropriate, in the investigator's judgment. Prior RLT is not allowed, though exceptions can be made following discussion with Novartis Medical Monitor. * Locally advanced, unresectable, or metastatic GEP-NEC, cervical NEC, genitourinary NEC, thymic NEC, Merkel cell carcinoma, or unknown primary NEC with disease progression following, or intolerance to, at least one line of systemic therapy (including platinum-containing chemotherapy for non-MCC indications, or PD-1 or PD-L1 inhibition for MCC, unless patient was ineligible to receive such therapy), and for whom no standard therapy is available, tolerated, or appropriate, in the investigator's judgment. * Locally advanced, unresectable, or metastatic medullary thyroid cancer with disease progression following, or intolerance to, at least 1 line of systemic therapy (unless patient was ineligible to receive such therapy), and for whom no standard therapy is available, tolerated, or appropriate, in the investigator's judgment. Dose expansion only: * Locally advanced, unresectable, or metastatic SCLC with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy (prior DLL3-targeted therapy allowed). Patients should have received no more than 2 prior lines of systemic therapy. * 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. 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. * 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. Exclusion Criteria: * Absolute neutrophil count (ANC) \< 1.0 x 10\^9/L, hemoglobin \< 9 g/dL, or platelet count \< 75 x 10\^9/L * QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec * eGFR \< 60 mL/min/1.73m2 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) * Any prior RLT (except for NEPC patients in expansion) Other protocol-defined inclusion/exclusion criteria may apply.

Interventions

DRUG

225Ac-ETN029

DRUG

111In-ETN029

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Small Cell Lung CarcinomaLarge Cell Neuroendocrine Carcinoma of the LungNeuroendocrine Prostate CancerGastroenteropancreatic Neuroendocrine CarcinomaNon-prostate Extrapulmonary Neuroendocrine CarcinomaCervical Neuroendocrine CarcinomaThymic Neuroendocrine CarcinomaGenitourinary Neuroendocrine CarcinomaUnknown Primary Neuroendocrine CarcinomasMerkel Cell CarcinomaMedullary Thyroid Carcinoma

Locations

University Of Iowa

Iowa City, Iowa 52242

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Corewell Health William Beaum Hosp

Royal Oak, Michigan 48073-6769

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington 98109-1024

United States

Novartis Investigative Site

Montreal, Quebec H3T 1E2

Canada

Novartis Investigative Site

Chuo Ku, Tokyo 1040045

Japan

Novartis Investigative Site

Seoul, Seoul 03080

South Korea

Novartis Investigative Site

Seoul, 03722

South Korea