A Safety Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) Patients in Combination With Carboplatin, Etoposide and Tislelizumab

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05142696
Collaborator
(none)
39
Enrollment
6
Arms
39.1
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to establish a safe and well tolerated dose of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide, and tislelizumab in induction treatment and with tislelizumab in maintenance treatment in newly diagnosed patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC).

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

The study for each participant consists of a Screening period, a Treatment period that includes an Induction treatment period and a Maintenance treatment period, and a Follow-up period.

During the screening period of up to 28 days before starting SCLC treatment, each participant will be assessed for somatostatin receptor (SSTR) expression by [68Ga]Ga-DOTA-TATE imaging PET/scan.

Eligible participants will be enrolled in cohorts of 3 to 6 participants to receive:
  • Four cycles of carboplatin area under the curve (AUC) 5 on Day 1 and etoposide 100 mg/m2 on Day 1-3, every 3 weeks at Weeks 1, 4, 7 and 10 in induction period

  • Tislelizumab 200 mg on Day 1 every 3 weeks in induction and maintenance period

  • Two administrations of [177Lu]Lu-DOTA-TATE during the induction period: on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 period followed by 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed.

Up to six different dose level combinations of [177Lu]Lu-DOTA-TATE will be assessed in the study as follows:

  • Dose Level 1 (DL1): 100 mCi of [177Lu]Lu-DOTA-TATE in the induction period and 100 mCi of [177Lu]Lu-DOTA-TATE in the maintenance period.

  • Dose Level 2a (DL2a): 150 mCi of [177Lu]Lu-DOTA-TATE in both the induction and the maintenance periods.

  • Dose Level 2b (DL2b): 150 mCi of [177Lu]Lu-DOTA-TATE in the induction period and 200 mCi of [177Lu]Lu-DOTA-TATE in the maintenance period.

  • Dose Level 3a (DL3a): 200 mCi of [177Lu]Lu-DOTA-TATE in both the induction and maintenance periods.

  • Dose Level 3b (DL3b): 200 mCi of [177Lu]Lu-DOTA-TATE in the induction period and 250 mCi of [177Lu]Lu-DOTA-TATE in the maintenance period.

  • Dose Level 4 (DL4): 250 mCi of [177Lu]Lu-DOTA-TATE in both the induction and maintenance periods.

An infusion of sterile 2.5% Lysine - Arginine amino acid (AA) solution will be co-administered with each [177Lu]Lu-DOTA-TATE dose for renal protection.

The dose escalation part in this study will be guided by the dose limiting toxicity (DLT) rate observed within the first 6 weeks (42 days) of treatment. In addition to DLTs the totality of safety data available at the time will be assessed for each dose escalation decision. Dose escalation/de escalation will be conducted using the Bayesian Optimal Interval Approach (BOIN).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
39 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) in Combination With Carboplatin, Etoposide and Tislelizumab in Induction and With Tislelizumab in Maintenance Treatment Phase
Anticipated Study Start Date :
Apr 20, 2022
Anticipated Primary Completion Date :
Jul 25, 2024
Anticipated Study Completion Date :
Jul 24, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dose Level 1 (DL1)

Dose Level 1 (DL1): [177Lu]Lu-DOTA-TATE 100 mCi Q6W with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 Q3W, and tislelizumab 200 mg Q3W in induction period, then [177Lu]Lu-DOTA-TATE 100 mCi Q3W plus Tislelizumab 200 mg Q3W in the maintenance period.

Drug: [177Lu]Lu-DOTA-TATE
Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
Other Names:
  • Lutathera
  • Lutetium (177Lu) oxodotreotide
  • Lutetium Lu 177 dotatate
  • Drug: Tislelizumab
    Tislelizumab 200 mg on Day 1 every 3 weeks in induction and maintenance period

    Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)

    Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Experimental: Dose Level 2a (DL2a)

    Dose Level 2a (DL2a): [177Lu]Lu-DOTA-TATE 150 mCi Q6W with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 Q3W, and tislelizumab 200 mg Q3W in induction period, then [177Lu]Lu-DOTA-TATE 150 mCi Q3W plus Tislelizumab 200 mg Q3W in the maintenance period.

    Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other Names:
  • Lutathera
  • Lutetium (177Lu) oxodotreotide
  • Lutetium Lu 177 dotatate
  • Drug: Tislelizumab
    Tislelizumab 200 mg on Day 1 every 3 weeks in induction and maintenance period

    Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)

    Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Experimental: Dose Level 2b (DL2b)

    Dose Level 2b (DL2b): [177Lu]Lu-DOTA-TATE 150 mCi Q6W with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 Q3W, and tislelizumab 200 mg Q3W in induction period, then [177Lu]Lu-DOTA-TATE 200 mCi Q3W plus Tislelizumab 200 mg Q3W in the maintenance period.

    Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other Names:
  • Lutathera
  • Lutetium (177Lu) oxodotreotide
  • Lutetium Lu 177 dotatate
  • Drug: Tislelizumab
    Tislelizumab 200 mg on Day 1 every 3 weeks in induction and maintenance period

    Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)

    Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Experimental: Dose Level 3a (DL3a)

    Dose Level 3a (DL3a): [177Lu]Lu-DOTA-TATE 200 mCi Q6W with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 Q3W, and tislelizumab 200 mg Q3W in induction period, then [177Lu]Lu-DOTA-TATE 200 mCi Q3W plus Tislelizumab 200 mg Q3W in the maintenance period.

    Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other Names:
  • Lutathera
  • Lutetium (177Lu) oxodotreotide
  • Lutetium Lu 177 dotatate
  • Drug: Tislelizumab
    Tislelizumab 200 mg on Day 1 every 3 weeks in induction and maintenance period

    Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)

    Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Experimental: Dose Level 3b (DL3b)

    Dose Level 3b (DL3b): [177Lu]Lu-DOTA-TATE 200 mCi Q6W with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 Q3W, and tislelizumab 200 mg Q3W in induction period, then [177Lu]Lu-DOTA-TATE 250 mCi Q3W plus Tislelizumab 200 mg Q3W in the maintenance period.

    Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other Names:
  • Lutathera
  • Lutetium (177Lu) oxodotreotide
  • Lutetium Lu 177 dotatate
  • Drug: Tislelizumab
    Tislelizumab 200 mg on Day 1 every 3 weeks in induction and maintenance period

    Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)

    Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Experimental: Dose Level 4 (DL4)

    Dose Level 4 (DL4): [177Lu]Lu-DOTA-TATE 250 mCi Q6W with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 Q3W, and tislelizumab 200 mg Q3W in induction period, then [177Lu]Lu-DOTA-TATE 250 mCi Q3W plus Tislelizumab 200 mg Q3W in the maintenance period.

    Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other Names:
  • Lutathera
  • Lutetium (177Lu) oxodotreotide
  • Lutetium Lu 177 dotatate
  • Drug: Tislelizumab
    Tislelizumab 200 mg on Day 1 every 3 weeks in induction and maintenance period

    Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)

    Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

    Outcome Measures

    Primary Outcome Measures

    1. Frequency of dose limiting toxicities (DLTs) [Within the first six weeks of [177Lu]Lu-DOTA-TATE treatment]

      A dose-limiting toxicity (DLT) is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications with an onset within the first 6 weeks (42 days) of treatment. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for AE grading.

    Secondary Outcome Measures

    1. Incidence and severity of adverse events (AEs), serious AEs (SAEs) after [177Lu]Lu-DOTA-TATE administration [From date of randomization till 30 days safety follow-up, assessed for up to 3 years (estimated final Overall Survival (OS) analysis)]

      The distribution of adverse events after [177Lu]Lu-DOTA-TATE administration will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

    2. Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs) within 48 hours after [68Ga]Ga-DOTA-TATE administration [up to 48 hours following the start of [68Ga]Ga-DOTA-TATE administration]

      The distribution of adverse events after [68Ga]Ga-DOTA-TATE administration will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

    3. Objective Response Rate (ORR) [From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis)]

      Objective response rate (ORR) is defined as the proportion of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1 by Investigator assessment. ORR will be calculated based on the Full Analysis Set (FAS). ORR and its 95% confidence interval will be presented by dose level combination.

    4. Duration of Response (DOR) [From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis)]

      Duration of response (DOR) only applies to participants whose best overall response is complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer. Participants continuing without progression or death due to underlying cancer will be censored at the date of their last adequate tumor assessment. DOR will be listed and summarized by dose level combination for all participants in the Full Analysis Set (FAS) with confirmed BOR of CR or PR.

    5. Progression Free Survival (PFS) [From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final OS analysis)]

      Progression Free Survival (PFS) is defined as the time from the date of first dose to the date of the first documented progression or death due to any cause. PFS will be assessed via local review according to RECIST 1.1. If no PFS event is observed, PFS will be censored at the date of the late adequate tumor assessment prior to data cut-off date and start of new anti-neoplastic therapy, whichever comes first. PFS will be analyzed in the Full Analysis Set (FAS) population according to the assigned dose level combination. The PFS distribution will be estimated using the Kaplan-Meier method, and the Kaplan-Meier curves, medians and 95% confidence intervals of the medians will be presented for each dose level combination.

    6. Overall Survival (OS) [From date of randomization until date of death from any cause, assessed up to 3 years (estimated final Overall Survival (OS) analysis)]

      Overall Survival (OS) is defined as the time from date of first dose to date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date). OS will be analyzed in the Full Analysis Set (FAS) population according to the assigned dose cohort. The OS distribution will be estimated using the Kaplan-Meier method, and the Kaplan-Meier curves, medians and 95% confidence intervals of the medians will be presented for each dose level combination.

    7. Time activity curves (TACs) [Week 7 Day 3]

      Time activity curves (TACs), describing percentage (%) of the activity injected vs time in blood, organs and tumor lesions

    8. Absorbed radiation doses of [177Lu]Lu-DOTA-TATE [Week 7 Day 3]

      Absorbed radiation doses of [177Lu]Lu-DOTA-TATE in organs and tumor lesions will be summarized with descriptive statistics.

    9. Concentration of [177Lu]Lu-DOTA-TATE in blood over time [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Blood samples for radioactivity measurement will be collected in all participants who undergo dosimetry assessments (i.e. first 3 participants at dose levels 1, 2a or 2b, 3a or 3b, and 4). For the rest of participants , blood samples will be taken before the start of [177Lu]Lu-DOTA-TATE infusion, at the end of infusion, and then at 2h, 6h after the end of [177Lu]Lu-DOTA-TATE infusion. Blood samples will be drawn in heparinized tubes. Radioactivity measurements on blood will be performed locally on site, using a gamma-counter.

    10. Observed maximum plasma concentration (Cmax) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics.

    11. Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Tmax will be listed and summarized using descriptive statistics.

    12. Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUClast will be listed and summarized using descriptive statistics.

    13. Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUCinf will be listed and summarized using descriptive statistics.

    14. Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. CL will be listed and summarized using descriptive statistics.

    15. Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics.

    16. Terminal elimination half-life (T^1/2) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics.

    17. Terminal-Phase Disposition Rate Constant (λz) of [177Lu]Lu-DOTA-TATE [Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)]

      Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Terminal-Phase Disposition Rate Constant will be listed and summarized using descriptive statistics.

    18. Quantification of [177Lu]Lu-DOTA-TATE excreted from the body in urine [Week 7 Day 3 with urine collection from the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging (1-3 hours after [177Lu]Lu-DOTA-TATE infusion)]

      All excreted urine from the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging will be collected, its volume measured and the radioactivity concentration (kBq/mL) determined in order to calculate the total radioactivity excreted from the body from the start of [177Lu]Lu-DOTA-TATE infusion to the time of the first scan. If no urine is excreted from the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging, no urine dosimetry is necessary.

    19. Serum concentrations of tislelizumab [Predose (within 60 minutes before starting tislelizumab infusion) samples are required to be collected on Day 1 of Week 1, 4, 13 and 25]

      Individual tislelizumab concentrations will be tabulated by dose cohort along with descriptive statistics.

    20. Number and percentage of participants who develop antidrug antibodies (ADAs) for tislelizumab [Predose (within 60 minutes before starting tislelizumab infusion) samples are required to be collected on Day 1 of Week 1, 4, 13 and 25]

      The incidence of positive ADAs and neutralizing ADAs will be reported for evaluable participants.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Participant is >= 18 years on the day of signing informed consent form

    • Histologically or cytologically confirmed ES-SCLC

    • Presence of measurable disease (at least one target lesion) according to RECIST v1.1 assessed by conventional computed tomography (CT) scan

    • SSTR positive [68Ga]Ga-DOTA-TATE imaging positron emission tomography (PET) scan demonstrating uptake in at least one target or non-target lesion

    • No prior systemic treatment for ES-SCLC

    • ECOG status =< 1

    • Provision of tumor tissue to support exploratory biomarker analysis

    • Life expectancy of >= 6 months

    Key Exclusion Criteria:
    • Participant has received prior therapy with an antibody or drug against immune checkpoint pathways

    • Active leptomeningeal disease or uncontrolled, untreated brain metastasis

    • Active autoimmune diseases or history of autoimmune diseases that may relapse

    • Severe chronic or active infections (including active tuberculosis, HBV, or HCV infection) requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks before Cycle 1 Day 1

    • Any major surgical procedure requiring general anesthesia =< 28 days before Cycle 1 Day 1

    • History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for participants participating in the study

    • Known hypersensitivity to the active substances or any of the excipients of the study drugs

    • Concurrent participation in another therapeutic clinical study

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT05142696
    Other Study ID Numbers:
    • CAAA601A42101
    • 2021-004155-16
    First Posted:
    Dec 2, 2021
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 6, 2022