Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors
A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors
2 other identifiers
interventional
116
3 countries
6
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2025
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 16, 2025
CompletedFirst Posted
Study publicly available on registry
June 5, 2025
CompletedStudy Start
First participant enrolled
October 16, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 29, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 29, 2031
May 5, 2026
May 1, 2026
5.9 years
May 16, 2025
May 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of patients with dose limiting toxicities of 225Ac-ETN029
A dose limiting toxicity (DLT) is defined as any adverse event or abnormal laboratory value of CTCAE 5.0 grade 3 or higher that occurs within the DLT evaluation period and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications with a few exceptions defined in the study protocol. Other significant toxicities may be considered to be DLTs, even if not Grade 3 or higher.
From the start of study treatment until 6 weeks after
Incidence and severity of adverse events and serious adverse events of 225Ac-ETN029
Incidence and severity of treatment-emergent adverse events and serious adverse events, including changes in laboratory values, vital signs, and electrocardiograms qualifying and reported as AEs
From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months
Dose modifications for 225Ac-ETN029
Number of dose modifications (e.g, dose interruptions and reductions) for 225Ac-ETN029
From the start of study treatment until last dose of study treatment, assessed as approximately 24 weeks
Dose intensity for 225Ac-ETN029
Dose intensity of 225Ac-ETN029 defined as the ratio of actual cumulative dose received and actual duration of exposure
From start of study treatment until last dose of study treatment, assessed as approximately 24 weeks
Secondary Outcomes (13)
Overall response rate (ORR)
Up to approximately 42 months
Disease control rate (DCR)
Up to approximately 42 months
Duration of response (DOR)
Up to approximately 42 months
Progression free survival (PFS)
Up to approximately 42 months
Area under the curve (AUC) of 225Ac-ETN029 and 111In-ETN029
During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration
- +8 more secondary outcomes
Study Arms (1)
Arm 1
EXPERIMENTALPatients will receive 225Ac-ETN029, with some patients also receiving 111In-ETN029
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
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
Seoul, 03080, South Korea
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 16, 2025
First Posted
June 5, 2025
Study Start
October 16, 2025
Primary Completion (Estimated)
August 29, 2031
Study Completion (Estimated)
August 29, 2031
Last Updated
May 5, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will not share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.