Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors
Purpose
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.
Conditions
- Small Cell Lung Carcinoma
- Large Cell Neuroendocrine Carcinoma of the Lung
- Neuroendocrine Prostate Cancer
- Gastroenteropancreatic Neuroendocrine Carcinoma
- Non-prostate Extrapulmonary Neuroendocrine Carcinoma
- Cervical Neuroendocrine Carcinoma
- Thymic Neuroendocrine Carcinoma
- Genitourinary Neuroendocrine Carcinoma
- Unknown Primary Neuroendocrine Carcinomas
- Merkel Cell Carcinoma
- Medullary Thyroid Carcinoma
Eligibility
- Eligible Ages
- Between 18 Years and 100 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1 |
Patients will receive 225Ac-ETN029, with some patients also receiving 111In-ETN029 |
|
Recruiting Locations
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
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.