A Dose Escalation and Expansion Study of [177Lu]Lu-SN201 in Participants With Advanced Cancer
- Conditions
- Solid TumorMetastatic CancerLocally Advanced Solid TumorUnresectable Solid TumorRecurrent Solid TumorRefractory Cancer
- Interventions
- Registration Number
- NCT06184035
- Lead Sponsor
- Spago Nanomedical AB
- Brief Summary
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.
- Detailed Description
Eligible participants will receive \[177Lu\]Lu-SN201 via slow intravenous infusion on Cycle 1 Day 1. Participants will initially receive one cycle of treatment and will progress to a 2nd and 3rd cycle of treatment, provided retreatment criteria are met before the start of each cycle. The dosing schedule visit frequency will be every 6 weeks (with an allowable window to delay each cycle by +3 weeks per retreatment criteria), each participant may receive up to 3 cycles, with the treatment duration up to 22 weeks. A total of 3 treatment cycles will be given unless the participant meets early discontinuation criteria. For Cycle 1, an overnight hospitalization for standard-of-care observation following Day 1 clinic assessments to Day 2 is mandatory for all participants receiving Cycle 1.
Whole-body planar imaging, and single photon emission computed tomography (SPECT)/computed tomography (CT) will be performed post-administration of \[177Lu\]Lu-SN201 to assess biodistribution and dosimetry. CT or magnetic resonance imaging (MRI) will be used to assess the response of the disease to treatment using Response Evaluation Criteria (RECIST v1.1).
The general procedures for participants in Phase I and Phase IIa are summarized below:
* Baseline values are defined as the last collected value prior to the start of infusion.
* Continual assessment of adverse events (AEs) and concomitant medication usage will be conducted.
* Whole-body planar on Day 1, Day 2, Day 4, and Day 8 and SPECT/CT on Day 2, Day 4 and Day 8 will be used for biodistribution and dosimetry evaluation of all participants. If dosimetry has been met by previous participants at each dose level, the DMC may partly or fully exclude the requirement for dosimetry procedures in remaining participants at this dose level.
* For participants that will continue to treatment Cycle 2 or 3, eligibility assessment and IMP procurement will take place within the coming 17 days.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase I/IIa Dose escalation and dose expansion [177Lu]Lu-SN201 Participants will initially receive 1 cycle of \[177Lu\]Lu-SN201 via slow intravenous infusion and progress to up to 3 cycles, provided retreatment criteria are met before the start of each cycle, occurring every 6 weeks (with an allowable window to delay each cycle by +3 weeks per retreatment criteria). Dose escalation: The study will evaluate up to 5 dose levels of \[177Lu\]Lu-SN201 (A1=10 MBq/kg, A2=25 MBq/kg, A=50 MBq/kg, A4= \<33% of A3, A5= \<33% of A4). Additional dose levels may be explored until MTD/RP2D is identified. Up to 9 participants may be enrolled at any pre-specified dose level shown to be tolerated for confirmation of MTD and/or RP2D. Dose expansion: Once the MTD/RP2D has been defined, an expansion phase consisting of multiple tumor types, each with up to 20 participants, will be enrolled to further characterize the safety, tolerability, and assess preliminary efficacy of \[177Lu\]Lu-SN201 at the RP2D and/or MTD identified in Phase I.
- Primary Outcome Measures
Name Time Method Phase I: Dose escalation to identify RP2D and/or MTD dose 24 months 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 24 months 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: Frequency and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) 48 months 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. 48 months 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.
- Secondary Outcome Measures
Name Time Method Phase I/IIa: Evaluation of clinical dosimetry 48 months 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/IIa: Measure plasma half-life of the [177Lu]Lu-SN201 activity 48 months 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 48 months Characterize the pharmacokinetic area under the curve vs time curve of the \[177Lu\]Lu-SN201 activity concentration in plasma over time
Phase I/IIa: Measure peak plasma [177Lu]Lu-SN201 activity concentration (Cmax) 48 months Characterize the pharmacokinetic Peak plasma concentration (Cmax) of the \[177Lu\]Lu-SN201 activity concentration over time
Phase IIa: Evaluation of clinical benefit based on disease control rates (DCR) 12 months 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).
Trial Locations
- Locations (2)
Cancer Research South Adelaide
🇦🇺Adelaide, South Australia, Australia
St Vincent Hospital Melbourne
🇦🇺Melbourne, Victoria, Australia