Phase Ib/II Study of Lutetium (177Lu) Oxodotreotide in Newly Diagnosed Extensive-Stage Small Cell Lung Cancer

The primary objectives of this study are to establish the recommended dose of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide, and atezolizumab during induction, and with atezolizumab during maintenance, in patients with newly diagnosed extensive stage small cell lung cancer. Additionally, the Phase II component aims to evaluate the efficacy of this combination therapy compared to the standard of care in terms of overall survival.

Secondary objectives include:

• Assessment of preliminary antitumor activity of the experimental regimen.
• Characterization of the pharmacokinetics and dosimetry of [177Lu]Lu-DOTA-TATE.
• Evaluation of the safety and tolerability of [177Lu]Lu-DOTA-TATE in combination with the specified induction and maintenance therapies.
• Assessment of the safety and tolerability of [68Ga]Ga-DOTA-TATE.

This clinical trial involves a total of 52 participants diagnosed with extensive stage small cell lung cancer. The study population includes both male and female individuals within specific age cohorts. Eligible participants must be at least 18 years of age and possess histologically or cytologically confirmed disease. Required clinical features include the presence of measurable disease according to RECIST v1.1 and SSTR positivity demonstrated via [68Ga]Ga-DOTA-TATE PET imaging with an uptake intensity score of 2 or higher. The population must have no prior systemic treatment for the malignancy, with the exception of the initial induction chemotherapy cycle. Additionally, participants are required to have a life expectancy of at least six months and provide tumor tissue for biomarker analysis.

This Phase Ib/II integrated clinical trial is designed to evaluate the safety and efficacy of lutetium (177lu) oxodotreotide in patients with newly diagnosed extensive stage small cell lung cancer. The first phase aims to establish the recommended dose of the investigational agent when combined with carboplatin, etoposide, and atezolizumab during the induction phase, followed by maintenance treatment with atezolizumab. The second phase is a controlled study to assess overall survival by comparing the experimental arm to a control arm receiving standard of care. The methodology involves a screening process to confirm histological diagnosis, presence of measurable disease via computed tomography, and SSTR positivity through positron emission tomography imaging. Participants will undergo induction and maintenance treatment phases, with primary endpoints in Phase Ib focusing on the frequency of dose limiting toxicities and adverse events. The study includes the monitoring of secondary endpoints such as progression-free survival and objective response rate. Involvement duration is subject to clinical progression or the achievement of study endpoints. Early termination may occur due to adverse events or other clinical criteria.

The experimental treatment includes lutetium (177Lu) oxodotreotide, provided as Lutathera 370 MBq/mL solution for infusion for intravenous infusion. Additionally, the study utilizes dotatate via NETSPOT, which is a kit for radiopharmaceutical preparation for intravenous use. Tislelizumab, administered as Tevimbra 100 mg concentrate for solution for infusion via intravenous infusion, is also utilized as a test substance.

The background therapy consists of atezolizumab administered via intravenous infusion. Chemotherapeutic agents include carboplatin and etoposide, both delivered by intravenous infusion. Arginine hydrochloride and lysine hydrochloride are provided as LysaKare 25 g/25 g solution for infusion for intravenous administration.

Efficacy assessment for extensive stage small cell lung cancer will be conducted across two phases. In Phase II, the primary efficacy endpoint is overall survival, which is defined as the time from the date of randomization to death due to any cause. Secondary efficacy endpoints in Phase II include progression-free survival, objective response rate, and duration of response, which are determined through investigator assessment according to RECIST 1.1.

During Phase Ib, efficacy and safety parameters include objective response rate, duration of response, progression-free survival, and overall survival. Additional assessments involve tumor absorbed radiation doses in organs and tumor lesions, the concentration of [177Lu]Lu-DOTA-TATE in blood over time with derived pharmacokinetic parameters, and the quantification of [177Lu]Lu-DOTA-TATE excreted in urine.