Recruiting
Phase 1

225Ac-ETN029, 111In-ETN029

Sponsor:

Novartis Pharmaceuticals

Code:

NCT07006727

Conditions

Small Cell Lung Carcinoma

Large Cell Neuroendocrine Carcinoma of the Lung

Neuroendocrine Prostate Cancer

Gastroenteropancreatic Neuroendocrine Carcinoma

Non-prostate Extrapulmonary Neuroendocrine Carcinoma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

225Ac-ETN029

111In-ETN029

Study Details

Brief 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.

Conditions

Small Cell Lung Carcinoma

Large Cell Neuroendocrine Carcinoma of the Lung

Neuroendocrine Prostate Cancer

Gastroenteropancreatic Neuroendocrine Carcinoma

Non-prostate Extrapulmonary Neuroendocrine Carcinoma

Study ID

NCT07006727

Start date

Oct 16, 2025

Status verified date

Sep, 2026

Completion date

Aug 29, 2031

Anticipated

Primary completion date

Aug 29, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

116 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1

Patients will receive 225Ac-ETN029, with some patients also receiving 111In-ETN029

Interventions

225Ac-ETN029

Radioligand therapy

111In-ETN029

Radioligand imaging agent

Primary outcome measure

  • Number of patients with dose limiting toxicities of 225Ac-ETN029 [ Time Frame: From the start of study treatment until 6 weeks after ]
  • Incidence and severity of adverse events and serious adverse events of 225Ac-ETN029 [ Time Frame: From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months ]
  • Dose modifications for 225Ac-ETN029 [ Time Frame: From the start of study treatment until last dose of study treatment, assessed as approximately 24 weeks ]
  • Dose intensity for 225Ac-ETN029 [ Time Frame: From start of study treatment until last dose of study treatment, assessed as approximately 24 weeks ]

Central Contacts and Locations

Central contacts

Novartis Pharmaceuticals

1-888-669-6682novartis.email@novartis.com

Novartis Pharmaceuticals

+41613241111novartis.email@novartis.com

Locations

University Of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Kellie Bodeker

+1 319 356 2197kellie-bodeker@uiowa.edu

Principal Investigator:

Yusuf Menda

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Beatrice Sears

bmsears@mgh.havard.edu

Principal Investigator:

Shadi Abdar Esfahani

Corewell Health William Beaum Hosp

Recruiting

Royal Oak, Michigan, United States, 48073-6769

Contacts

Matthew Johnson

+1 248 898 2697matthew.johnson3@corewellhealth.org

Principal Investigator:

Andrew Thompson

Fred Hutchinson Cancer Research Center

Recruiting

Seattle, Washington, United States, 98109-1024

Contacts

Heather White

hwhite@fredhutch.org

Principal Investigator:

Delphine Chen

Novartis Investigative Site

Recruiting

Montreal, Quebec, Canada, H3T 1E2

More Information

Sponsor

Novartis Pharmaceuticals

Last update posted

Sep 22, 2026

Last verified

Sep, 2026

Keywords

  • Small Cell Lung Carcinoma (SCLC)
  • Large Cell Neuroendocrine Carcinoma of the Lung (LCNEC)
  • Neuroendocrine Prostate Cancer (NEPC)
  • Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)
  • Cervical Neuroendocrine Carcinoma
  • Thymic Neuroendocrine Carcinoma
  • Genitourinary Neuroendocrine Carcinoma (GU-NEC)
  • Unknown Primary Neuroendocrine Carcinomas
  • Merkel cell carcinoma (MCC)
  • Medullary thyroid carcinoma (MTC)
  • DLL3
  • Neuroendocrine neoplasms
  • Radioligand therapy (RLT)
  • [225Ac]Ac-ETN029
  • [111In]In-ETN029

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Novartis Pharmaceuticals on 2026-09-22. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.