Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: 225Ac-ETN029, 111In-ETN029.
- Who it may be relevant to
- Registry conditions: Small Cell Lung Carcinoma, Large Cell Neuroendocrine Carcinoma of the Lung, Neuroendocrine Prostate Cancer, Gastroenteropancreatic Neuroendocrine Carcinoma. Basic parameters: 18 years — 100 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Canada, South Korea
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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.
Detailed description
This is a phase I, open-label, multi-center study to evaluate the safety, tolerability, dosimetry, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of 225Ac-ETN029 in patients with advanced DLL3-expressing solid tumors. The study consists of a dose escalation part, followed by a dose expansion part. Once the recommended radioactive dose(s) of 225Ac-ETN029 for further clinical evaluation are determined, the dose expansion part will further characterize the safety, tolerability, and preliminary anti-tumor activity of 225Ac-ETN029. The study will also enable an initial evaluation of the safety, dosimetry, PK, and imaging properties of 111In-ETN029.
Interventions
- Drug 225Ac-ETN029
Radioligand therapy - Drug 111In-ETN029
Radioligand imaging agent
Primary outcome measures
- Number of patients with dose limiting toxicities of 225Ac-ETN029 [Time frame: From the start of study treatment until 6 weeks after]
- 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]
- Dose modifications for 225Ac-ETN029 [Time frame: From the start of study treatment until last dose of study treatment, assessed as approximately 24 weeks]
- Dose intensity for 225Ac-ETN029 [Time frame: From start of study treatment until last dose of study treatment, assessed as approximately 24 weeks]
Secondary outcome measures (12)
- Overall response rate (ORR) [Time frame: Up to approximately 42 months]
- Disease control rate (DCR) [Time frame: Up to approximately 42 months]
- Duration of response (DOR) [Time frame: Up to approximately 42 months]
- Progression free survival (PFS) [Time frame: Up to approximately 42 months]
- Area under the curve (AUC) of 225Ac-ETN029 and 111In-ETN029 [Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
- Observed maximum blood concentration (Cmax) of 225Ac-ETN029 and 111In-ETN029 [Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
- Volume of distribution (Vz) of 225Ac-ETN029 and 111In-ETN029 during the terminal phase [Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
- Terminal elimination half-life (T1/2) of 225Ac-ETN029 and 111In-ETN029 [Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
- Total body clearance of 225Ac-ETN029 and 111In-ETN029 [Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
- Observed maximum radioactivity concentration (Rmax) of 225Ac-ETN029 [Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
- Absorbed dose of 225Ac-ETN029 and 111In-ETN029 [Time frame: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
- Incidence and severity of adverse events and serious adverse events of 111In-ETN029 [Time frame: From the start of 111In-ETN029 to the day before the first 225Ac-ETN029 administration or until the completion of 30 day follow up (assessed as approximately 30 days)]
Eligibility 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 4 centers
- University Of Iowa — Iowa City
- Massachusetts General Hospital — Boston
- Corewell Health William Beaum Hosp — Royal Oak
- Fred Hutchinson Cancer Research Center — Seattle
South Korea · 2 centers
- Novartis Investigative Site — Seoul
- Novartis Investigative Site — Seoul
Canada · 1 center
- Novartis Investigative Site — Montreal
Identifiers
NCT: NCT07006727 · CESP359A12101 · 2024-519111-34-00