Phase I testing of 225Ac-ETN029 for advanced DLL3-positive tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is an open-label, multi-center Phase I trial using a dose-escalation then dose-expansion design to determine the recommended radioactive dose(s) of 225Ac-ETN029. The study will collect safety, tolerability, dosimetry, pharmacokinetics, pharmacodynamics, and preliminary efficacy data, with 111In-ETN029 used to characterize imaging and biodistribution. Adults with locally advanced or metastatic DLL3-expressing tumors (including SCLC, LCNEC, NEPC, and GEP-NEC) are eligible under specified prior-therapy criteria. Results will guide further development of this DLL3-targeted alpha-emitter approach.

Why it matters

Who can join: the full rules

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.

Where it's running

• University Of Iowa
  Iowa City, Iowa, United States Recruiting
• Massachusetts General Hospital
  Boston, Massachusetts, United States Recruiting
• Corewell Health William Beaum Hosp
  Royal Oak, Michigan, United States Recruiting
• Fred Hutchinson Cancer Research Center
  Seattle, Washington, United States Recruiting
• Novartis Investigative Site
  Montreal, Quebec, Canada Recruiting
• Novartis Investigative Site
  Chuo Ku, Tokyo, Japan Recruiting

Study contacts

• Study coordinator: Novartis Pharmaceuticals
• Email: novartis.email@novartis.com
• Phone: 1-888-669-6682

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.