The purpose of this first-in-human (FIH) study is to determine the maximum tolerated dose (MTD) and to characterize the safety, tolerability, PK, and dosimetry profile of \[177Lu\]Lu-SN201 in adult participants with advanced solid tumors who have no standard of care treatment options.
\[177Lu\]Lu-SN201 is a radiolabeled, nanomedical investigational medicinal product (IMP) whose mechanism of delivery is based on the Enhanced Permeability and Retention (EPR) effect.
Male or female participants ≥ 18 years of age on the day of signing informed consent.
Histologically or cytologically documented, recurrent, locally advanced, or metastatic solid malignancy that has failed at least one prior systemic standard therapy, or for which standard therapy is not appropriate, or for which no standard therapy exists.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Life expectancy ≥ 3 months.
Unstable systemic disease (including but not limited to active infection, hepatic, renal, or metabolic disease).
Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2).
LVEF of < 50%, as determined by MUGA or ECHO.
Uncontrolled hypertension, defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy.
Single group
[177Lu]Lu-SN201
DrugIntravenous infusion
Phase I/IIa: Frequency and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Clinically significant safety laboratory results will be graded by NCI CTCAE v5.0. AEs (including physical examination, vital signs, ECG, and safety lab findings), related AEs, DLTs, SAEs, and related SAEs, AEs with NCI CTCAE Grades ≥ 3, AEs leading to premature discontinuation, interruptions, duration of interruptions and discontinuation of IRP will be analyzed descriptively utilizing corresponding Medical Dictionary for Regulatory Activities System Organ Classes and Preferred Terms. NCI CTCAE v5.0 toxicity grades will be utilized for classifying severity. Continual assessment of adverse events (AEs) and concomitant medication usage will be conducted.
Phase I/IIa: Incidence of Dose-Limiting Toxicity (DLT) during the first cycle of treatment.
DLTs are defined as: * Any Grade ≥ 3 AEs of any etiology that are clinically significant and last \> 7 days except: * Nausea, vomiting, or diarrhea will be considered a DLT only if it persists at Grade ≥ 3 for \> 3 days despite adequate supportive care measures. At the Investigator's discretion, participants who experience nausea, vomiting, or diarrhea after receiving IMP may receive antiemetic or anti-diarrheal medication before subsequent doses of IMP. * Isolated laboratory abnormalities Grade ≥ 3 (not present at Baseline) that are not considered to be significant by the Investigator and are resolved to at least Grade 1 within 7 days without clinical sequelae or need for therapeutic intervention. * Any other toxicity occurring at any time during the study that in the view of the participating Investigators and the Medical Monitor represents a clinically significant hazard to the participant. DLTs will be confirmed by the DMC.
Phase I: Dose escalation to identify RP2D and/or MTD dose
RP2D and/or MTD will be based on the DLT rate. Dose escalation will follow BOIN design, directed by the DLT rate (the current number of participants with DLT divided by the current number of participants in the cohort). The study will evaluate up to 5 dose levels of \[177Lu\]Lu-SN201, however additional dose levels may be explored until MTD/RP2D is identified. If the starting dose is not tolerated, a lower dose may be evaluated based on toxicity, safety, pharmacokinetics, and dosimetry data as determined by the DMC.
Phase IIa: Clinical benefit in solid tumor subgroups at RP2D and/or MTD
Clinical benefit according to RECIST v1.1 of \[177Lu\]Lu-SN201, as defined by post-treatment tumor response and serum levels of applicable tumor markers, compared to baseline (last collected value/measurement before the start of treatment)
Phase I/IIa: Measure peak plasma [177Lu]Lu-SN201 activity concentration (Cmax)
Characterize the pharmacokinetic Peak plasma concentration (Cmax) of the \[177Lu\]Lu-SN201 activity concentration over time
Phase I/IIa: Measure plasma half-life of the [177Lu]Lu-SN201 activity
Characterize the pharmacokinetic half-life of the \[177Lu\]Lu-SN201 activity concentration over time in plasma
Phase I/IIa: Measure the area under the plasma concentration versus time curve (AUC) of [177Lu]Lu-SN201 activity
Characterize the pharmacokinetic area under the curve vs time curve of the \[177Lu\]Lu-SN201 activity concentration in plasma over time
Phase I/IIa: Evaluation of clinical dosimetry
To evaluate clinical dosimetry with whole-body planar and SPECT/CT imaging modalities to asses percentage injected dose of activity concentration and distribution of \[177Lu\]Lu-SN201 in tumor and organs.
Phase I: Evaluation of clinical benefit based on disease control rates (DCR)
To evaluate clinical benefit based disease control rates (DCR) according to RECIST v1.1; * Overall Response Rate (ORR). * Duration of response (DoR). * Progression-free survival (PFS). * Overall survival (OS).
Phase I: Characterization of early signs of efficacy in tumor-type subgroups
Up to 3 subgroups will be selected for the Phase IIa part of the study, based on emerging data on early signs of efficacy, and discussions with Clinical Investigators and Sponsor representatives.
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