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
Summary
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.
Arms & interventions
- Drug225Ac-ETN029
Radioligand therapy
- Drug111In-ETN029
Radioligand imaging agent
Outcome measures
Primary
Number of patients with dose limiting toxicities of 225Ac-ETN029
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.
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
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
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
Number of dose modifications (e.g, dose interruptions and reductions) 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
Dose intensity of 225Ac-ETN029 defined as the ratio of actual cumulative dose received and actual duration of exposure
Time frame: From start of study treatment until last dose of study treatment, assessed as approximately 24 weeks
Secondary
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)
Visual and quantitative assessment of 111In-ETN029 uptake in normal tissues over time
Time frame: During the first ~5 days following 111In-ETN029 administration
Eligibility criteria
Study locations (4)
University Of Iowa
Iowa City, Iowa, 52242
Massachusetts General Hospital
Boston, Massachusetts, 02114
Corewell Health William Beaum Hosp
Royal Oak, Michigan, 48073-6769
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024