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

ConditionsSmall Cell Lung CarcinomaLarge Cell Neuroendocrine Carcinoma of the LungNeuroendocrine Prostate CancerGastroenteropancreatic Neuroendocrine CarcinomaNon-prostate Extrapulmonary Neuroendocrine CarcinomaCervical Neuroendocrine CarcinomaThymic Neuroendocrine CarcinomaGenitourinary Neuroendocrine CarcinomaUnknown Primary Neuroendocrine CarcinomasMerkel Cell CarcinomaMedullary Thyroid Carcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-100
SponsorNovartis Pharmaceuticals

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years old

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • 225Ac-ETN029

    Drug

    Radioligand therapy

  • 111In-ETN029

    Drug

    Radioligand imaging agent

Treatment groups

116 Participants
are divided into 1 treatment group
Group A: Arm 1Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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
2

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
3

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
4

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 outcomes

1

Overall response rate (ORR)

ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.

Time frame
Up to approximately 42 months
2

Disease control rate (DCR)

DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease according to RECIST v1.1 guidelines.

Time frame
Up to approximately 42 months
3

Duration of response (DOR)

DOR is defined as the time between the first documented response (CR or PR) and the date of progression according to RECIST v1.1 guidelines, or death due to any cause.

Time frame
Up to approximately 42 months
4

Progression free survival (PFS)

PFS is defined as the time from the date of start of treatment to the date of the first documented progression according to RECIST v1.1 guidelines or death due to any cause.

Time frame
Up to approximately 42 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Novartis Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov
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