A phase I, open-label, multi-center study to evaluate the safety, tolerability, dosimetry, and preliminary activity of [Ac225]Ac-ETN029 in patients with advanced DLL3-expressing solid tumors (CESP359A12101)
Phase I study of [225Ac]Ac-ETN029 in patients with advanced DLL3-expressing solid tumors (CESP359A12101)
Moizumi Sanae
Novartis Pharma. K.K.
Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan
+81-120-003-293
rinshoshiken.toroku2@novartis.com
Moizumi Sanae
Novartis Pharma. K.K.
Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan
+81-120-003-293
rinshoshiken.toroku2@novartis.com
Pending
July. 31, 2026
6
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
- 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.
- 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)
- Number of patients with dose limiting toxicities of 225Ac-ETN029 [Time Frame: From the start of study treatment until 6 weeks after]
- 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.
- Incidence and severity of adverse events and serious adverse events of 225Ac-ETN029 [Time Frame: From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months]
- 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
- Dose modifications for 225Ac-ETN029 [Time Frame: From the start of study treatment until last dose of study treatment, assessed as approximately 24 weeks]
- Number of dose modifications (e.g, dose interruptions and reductions) for 225Ac-ETN029
- Dose intensity for 225Ac-ETN029 [Time Frame: From start of study treatment until last dose of study treatment, assessed as approximately 24 weeks]
- Dose intensity of 225Ac-ETN029 defined as the ratio of actual cumulative dose received and actual duration of exposure
