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

NCT07006727 · Novartis
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Official title
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
About this study
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
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.
Study design
Enrollment target: 116 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-10-16
Estimated completion: 2031-08-29
Last updated: 2026-05-05
Interventions
Drug: 225Ac-ETN029Drug: 111In-ETN029
Primary outcomes
  • Number of patients with dose limiting toxicities of 225Ac-ETN029 (From the start of study treatment until 6 weeks after)
  • Incidence and severity of adverse events and serious adverse events of 225Ac-ETN029 (From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months)
  • Dose modifications for 225Ac-ETN029 (From the start of study treatment until last dose of study treatment, assessed as approximately 24 weeks)
Sponsor
Novartis Pharmaceuticals · industry
Contacts & investigators
ContactNovartis Pharmaceuticals · contact · novartis.email@novartis.com · 1-888-669-6682
ContactNovartis Pharmaceuticals · contact · novartis.email@novartis.com · +41613241111
All locations (6)
University Of IowaRecruiting
Iowa City, Iowa, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Corewell Health William Beaum HospRecruiting
Royal Oak, Michigan, United States
Fred Hutchinson Cancer Research CenterRecruiting
Seattle, Washington, United States
Novartis Investigative SiteRecruiting
Montreal, Quebec, Canada
Novartis Investigative SiteRecruiting
Seoul, South Korea
Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors · TrialPath