Phase I testing of 225Ac-ETN029 for advanced DLL3-positive 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
This trial will test 225Ac-ETN029, with 111In-ETN029 used for imaging, to see if the treatment is safe, tolerable, and shows early anti-tumor activity in adults with advanced DLL3-positive neuroendocrine cancers.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 116 (estimated) |
| Ages | 18 Years to 100 Years |
| Sex | All |
| Sponsor | Novartis Industry-sponsored |
| Drugs / interventions | chemotherapy |
| Locations | 6 sites (Iowa City, Iowa and 5 other locations) |
| Trial ID | NCT07006727 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Adults (≥18) with locally advanced or metastatic DLL3-positive SCLC, LCNEC (dose escalation), NEPC, or GEP-NEC who have progressed on or are intolerant to prior systemic therapies and meet baseline organ function and safety criteria are the intended participants.
Not a fit: Patients whose tumors lack DLL3 expression, who have poor organ function or uncontrolled comorbidities, who are pregnant, or who have very early-stage disease are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, this targeted alpha-emitter therapy could shrink tumors or control disease in DLL3-positive cancers while limiting radiation exposure to surrounding tissues.
How similar studies have performed: Previous DLL3-targeted antibody-drug conjugates showed limited success in larger trials, whereas targeted radioligand therapies for other neuroendocrine targets (e.g., 177Lu-DOTATATE) have been effective, making DLL3-targeted alpha therapy a novel and early approach with unproven but plausible potential.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Iowa City, Iowa and 5 other locations
- 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 — Seoul, South Korea (Recruiting)
Study contacts
- Study coordinator: Novartis Pharmaceuticals
- Email: novartis.email@novartis.com
- Phone: 1-888-669-6682
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.