phase i study of [225ac]ac-etn029 in patients with advanced dll3-expressing solid tumors

Conditions: Small Cell Lung Carcinoma; Large Cell Neuroendocrine Carcinoma of the Lung; Neuroendocrine Prostate Cancer; Gastroenteropancreatic Neuroendocrine Carcinoma

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.

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.

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.

Keywords: small cell lung carcinoma (sclc) large cell neuroendocrine carcinoma of the lung (lcnec) neuroendocrine prostate cancer (nepc) gastroenteropancreatic neuroendocrine carcinoma (gep-nec) dll3 neuroendocrine neoplasms radioligand therapy (rlt) [225ac]ac-etn029 [111in]in-etn029