RecruitingPhase 1

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 100 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This early study tests [225Ac]Ac-ETN029 in adults with advanced cancers that have a protein called DLL3. It checks safety, side effects, radiation doses, and early signs that treatment works. It also tests the safety of [111In]In-ETN029 and how well it helps show tumors on scans.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • You must be age 18 or older and have an eligible advanced cancer with DLL3.
  • Eligible lung cancers include small cell lung cancer and large cell neuroendocrine cancer. Neuroendocrine cancers start in cells with nerve-like and hormone-making features.
  • Other eligible cancers include certain neuroendocrine cancers of the prostate, digestive system, cervix, urinary or reproductive organs, thymus, or an unknown starting site. Merkel cell skin cancer and medullary thyroid cancer may also qualify.
  • Most groups must have cancer that got worse after treatment or treatment side effects they could not tolerate. The required past treatments depend on the cancer type.
  • Some groups must have no standard treatment that is available, suitable, or tolerable.
  • In the dose-expansion part, which tests selected doses in more people, only small cell lung cancer and certain digestive-system or prostate neuroendocrine cancers qualify. Small cell lung cancer patients may have had no more than 2 past courses of whole-body treatment.
  • In dose expansion, digestive-system and prostate neuroendocrine cancers must have at least one tumor that can be measured and takes up more [111In]In-ETN029 than nearby tissue on a scan.
  • Prostate neuroendocrine cancer must be confirmed by tissue testing. Dose expansion also requires tests for markers of this cancer.

Who can't join

  • Blood counts below these limits: neutrophils, infection-fighting cells, below 1.0 × 10^9/L; hemoglobin, which carries oxygen, below 9 g/dL; or platelets, which help blood clot, below 75 × 10^9/L.
  • A heart test showing a corrected QT interval of 470 milliseconds or more. This measures part of the heart's electrical recovery between beats.
  • A kidney filtering rate, called eGFR, below 60 mL/min/1.73 m².
  • A urinary blockage or trouble controlling urine that cannot be managed.
  • Cancer in the lining around the brain or spinal cord, or cancer spread to the brain or spinal cord that causes symptoms or needs treatment aimed at that area.
  • Current or past lung tissue disease or lung inflammation rated grade 2 or higher.
  • Past treatment aimed at DLL3, unless you have small cell lung cancer.
  • Past radioligand therapy, which delivers radiation to targeted cells. Some prostate neuroendocrine cancer patients in dose expansion may qualify; exceptions in dose escalation require discussion with the study's medical monitor.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 sites (4)

IA

MA

MI

WA