TheranosticTrials.org

Clinical Trial · NCT07006727

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

Overview

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.

Sponsor

Novartis

Phase

Phase 1

ClinicalTrials.gov

NCT07006727

Study contact

Novartis Pharmaceuticals

novartis.email@novartis.com 1-888-669-6682

Drug / Compound

[225Ac]Ac-ETN029

Isotope(s):
Target(s):
  • DLL3

Eligibility

Inclusion

  • 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.
  • Patients with one of the following indications: Dose Escalation Only:
  • 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 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.
  • LCNEC of the lung with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy.
  • 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 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.
  • 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).

Exclusion

  • Any prior RLT (except for NEPC patients in expansion) Other protocol-defined inclusion/exclusion criteria may apply.
  • QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec
  • Absolute neutrophil count (ANC) \< 1.0 x 10\^9/L, hemoglobin \< 9 g/dL, or platelet count \< 75 x 10\^9/L
  • Any prior DLL3-targeted therapy (except for SCLC)
  • Presence of leptomeningeal disease, of symptomatic CNS metastases or of CNS metastases that require local CNS-directed therapy
  • Unmanageable urinary tract obstruction or urinary incontinence
  • eGFR \< 60 mL/min/1.73m2 calculated using the CKD-EPI 2021 formula or measured
  • History of or current interstitial lung disease or pneumonitis ≥ Grade 2