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RecruitingInterventionalPhase 1

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

NCT ID: NCT07006727Sponsor: Novartis PharmaceuticalsLast updated: 2026-05-05

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.

Arms & interventions

  • Drug225Ac-ETN029

    Radioligand therapy

  • Drug111In-ETN029

    Radioligand imaging agent

Outcome measures

Primary

  • 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.

    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

    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

    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

    Number of dose modifications (e.g, dose interruptions and reductions) 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

    Dose intensity of 225Ac-ETN029 defined as the ratio of actual cumulative dose received and actual duration of exposure

    Time frame: From start of study treatment until last dose of study treatment, assessed as approximately 24 weeks

Secondary

  • Overall response rate (ORR)

    Time frame: Up to approximately 42 months

  • Disease control rate (DCR)

    Time frame: Up to approximately 42 months

  • Duration of response (DOR)

    Time frame: Up to approximately 42 months

  • Progression free survival (PFS)

    Time frame: Up to approximately 42 months

  • Area under the curve (AUC) of 225Ac-ETN029 and 111In-ETN029

    Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration

  • Observed maximum blood concentration (Cmax) of 225Ac-ETN029 and 111In-ETN029

    Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration

  • Volume of distribution (Vz) of 225Ac-ETN029 and 111In-ETN029 during the terminal phase

    Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration

  • Terminal elimination half-life (T1/2) of 225Ac-ETN029 and 111In-ETN029

    Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration

  • Total body clearance of 225Ac-ETN029 and 111In-ETN029

    Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration

  • Observed maximum radioactivity concentration (Rmax) of 225Ac-ETN029

    Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration

  • Absorbed dose of 225Ac-ETN029 and 111In-ETN029

    Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration

  • Incidence and severity of adverse events and serious adverse events of 111In-ETN029

    Time frame: From the start of 111In-ETN029 to the day before the first 225Ac-ETN029 administration or until the completion of 30 day follow up (assessed as approximately 30 days)

  • Visual and quantitative assessment of 111In-ETN029 uptake in normal tissues over time

    Time frame: During the first ~5 days following 111In-ETN029 administration

Eligibility criteria

Sex: AllAge: 18 Years to 100 YearsHealthy volunteers: No
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 locations (4)

University Of Iowa

Iowa City, Iowa, 52242

Recruiting
Kellie Bodeker · Contact
Yusuf Menda · Principal Investigator

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Mingyuan Tommy Song · Contact
Shadi Abdar Esfahani · Principal Investigator

Corewell Health William Beaum Hosp

Royal Oak, Michigan, 48073-6769

Recruiting
Andrew Thompson · Principal Investigator

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024

Recruiting
Akshata Mathur · Contact
Delphine Chen · Principal Investigator