Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 225Ac-ETN029
  Radioligand therapy
• Препарат 111In-ETN029
  Radioligand imaging agent

Первичные конечные точки

• Number of patients with dose limiting toxicities of 225Ac-ETN029 [Срок оценки: From the start of study treatment until 6 weeks after]
• Incidence and severity of adverse events and serious adverse events of 225Ac-ETN029 [Срок оценки: From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months]
• Dose modifications for 225Ac-ETN029 [Срок оценки: From the start of study treatment until last dose of study treatment, assessed as approximately 24 weeks]
• Dose intensity for 225Ac-ETN029 [Срок оценки: From start of study treatment until last dose of study treatment, assessed as approximately 24 weeks]

Вторичные конечные точки (12)

• Overall response rate (ORR) [Срок оценки: Up to approximately 42 months]
• Disease control rate (DCR) [Срок оценки: Up to approximately 42 months]
• Duration of response (DOR) [Срок оценки: Up to approximately 42 months]
• Progression free survival (PFS) [Срок оценки: Up to approximately 42 months]
• Area under the curve (AUC) of 225Ac-ETN029 and 111In-ETN029 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
• Observed maximum radioactivity concentration (Rmax) of 225Ac-ETN029 [Срок оценки: During the first ~14 days following 225Ac-ETN029 administration and ~5 days following 111In-ETN029 administration]
• Absorbed dose of 225Ac-ETN029 and 111In-ETN029 [Срок оценки: 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 [Срок оценки: 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)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• 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 центра

• Novartis Investigative Site — Seoul
• Novartis Investigative Site — Seoul

Канада · 1 центр

• Novartis Investigative Site — Montreal

Идентификаторы

NCT: NCT07006727 · CESP359A12101 · 2024-519111-34-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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