MedPath

A Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed ES-SCLC Patients in Combination With Carboplatin, Etoposide and Atezolizumab

Phase 1
Recruiting
Conditions
Extensive Stage Small Cell Lung Cancer
Interventions
Drug: [177Lu]Lu-DOTA-TATE
Drug: Atezolizumab
Drug: [68Ga]Ga-DOTA-TATE
Other: Carboplatin
Other: Etoposide
Registration Number
NCT05142696
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This study aims to establish a safe and well tolerated dose of \[177Lu\]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in this setting and to assess preliminary efficacy of this combination treatment versus the combination of carboplatin, etoposide, and atezolizumab.The study will be essential to assess a new potential therapeutic option in participants with this aggressive cancer type.

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.

The study will consist of a Phase Ib dose escalation with concurrent backfill part and a randomised controlled Phase II part.

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.

The dose escalation part in this study will be guided by the dose limiting toxicity (DLT) rate observed during the DLT period. To achieve a more robust dataset and to aid dose decisions, additional participants may be backfilled in each dose level.

Upon dedclaring RD, a 1:1 randomised Phase II with approximately 140 participants with newly diagnosed ES-SCLC will be enrolled and receive either \[177Lu\]Lu-DOTA-TATE at the RD in combination with carboplatin, etoposide and atezolizumab (experimental arm) or carboplatin, etoposide and atezolizumab alone (control arm).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
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
  • No prior systemic treatment for ES-SCLC (except the first cycle of chemotherapy with or without atezolizumab of the induction period
  • ECOG status =< 1
  • Provision of tumor tissue to support exploratory biomarker analysis
  • Life expectancy of >= 6 months

Key

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose Level 1 (DL1)[177Lu]Lu-DOTA-TATEDose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 1 (DL1)EtoposideDose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 1 (DL1)CarboplatinDose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 2a (DL2a)CarboplatinDose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 3a (DL3a)EtoposideDose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 2a (DL2a)[177Lu]Lu-DOTA-TATEDose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 2a (DL2a)[68Ga]Ga-DOTA-TATEDose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 2b (DL2b)[177Lu]Lu-DOTA-TATEDose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.
Dose Level 3a (DL3a)CarboplatinDose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 2b (DL2b)[68Ga]Ga-DOTA-TATEDose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.
Dose Level 2b (DL2b)CarboplatinDose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.
Dose Level 2b (DL2b)EtoposideDose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.
Dose Level 3b (DL3b)CarboplatinDose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 4 (DL4)CarboplatinDose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 1 (DL1)[68Ga]Ga-DOTA-TATEDose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 4 (DL4)EtoposideDose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Phase II Experimental arm[68Ga]Ga-DOTA-TATE\[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)
Dose Level 2a (DL2a)EtoposideDose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 3a (DL3a)[177Lu]Lu-DOTA-TATEDose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 3a (DL3a)[68Ga]Ga-DOTA-TATEDose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 3b (DL3b)[177Lu]Lu-DOTA-TATEDose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 3b (DL3b)[68Ga]Ga-DOTA-TATEDose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Phase II Experimental armEtoposide\[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)
Dose Level 3b (DL3b)EtoposideDose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 4 (DL4)[177Lu]Lu-DOTA-TATEDose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 4 (DL4)[68Ga]Ga-DOTA-TATEDose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Phase II Control armEtoposideCarboplatin, etoposide and atezolizumab alone (control arm)
Phase II Experimental armCarboplatin\[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)
Phase II Control arm[68Ga]Ga-DOTA-TATECarboplatin, etoposide and atezolizumab alone (control arm)
Phase II Control armCarboplatinCarboplatin, etoposide and atezolizumab alone (control arm)
Dose Level 1 (DL1)AtezolizumabDose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 2a (DL2a)AtezolizumabDose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 2b (DL2b)AtezolizumabDose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.
Dose Level 3a (DL3a)AtezolizumabDose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 3b (DL3b)AtezolizumabDose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Dose Level 4 (DL4)AtezolizumabDose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
Phase II Control armAtezolizumabCarboplatin, etoposide and atezolizumab alone (control arm)
Phase II Experimental armAtezolizumab\[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)
Primary Outcome Measures
NameTimeMethod
Phase ll: Overall survival (OS)In the phase II part: From date of randomization until date of death from any cause, assessed up to 3 years (estimated final Overall Survival (OS) analysis)

OS is defined as time from date of randomization to death due to any cause.

Phase 1b: Frequency of dose limiting toxicities (DLTs), Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to treatment discontinuationWithin 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 cycle of initiation of \[177Lu\]Lu-DOTA-TATE 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
NameTimeMethod
Phase ll: Duration of Response (DOR) by investigator assessmentFrom 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), calculated as the time from the date of the first documented CR or PR to 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 and checkpoint inhibitor in Phase Ib and by treatment group in Phase II part for all participants in the FAS with confirmed BOR of CR or PR.

Observed maximum plasma concentration (Cmax) of [177Lu]Lu-DOTA-TATEWeek 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.

Phase lb: Objective Response Rate (ORR) based on Investigator assessmentFrom 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 percentage of participants with confirmed best overall confirmed 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 FAS. ORR and its 95% confidence interval will be presented by dose level combination and checkpoint inhibitor in Phase Ib and by treatment group in Phase II part.

Phase lb: Absorbed radiation doses of [177Lu]Lu-DOTA-TATEWeek 7 Day 3

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

Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATEWeek 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.

Phase ll: Progression free survival (PFS) by investigator assessmentFrom 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.

Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-DOTA-TATEWeek 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.

Phase lb: 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), calculated as the time from the date of the first documented CR or PR to 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 and checkpoint inhibitor in Phase Ib and by treatment group in Phase II part for all participants in the FAS with confirmed BOR of CR or PR.

Phase lb: Time activity curves (TACs)Week 7 Day 3

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

Phase lb: Concentration of [177Lu]Lu-DOTA-TATE in blood over timeWeek 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.

Phase lb: Progression Free Survival (PFS) based on Investigator assessmentFrom 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 FAS population according to the assigned dose level combination and checkpoint inhibitor in Phase Ib and by treatment group in Phase II part. 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 and checkpoint inhibitor in Phase Ib and by treatment group in Phase II part.

Phase lb: 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)

OS is defined as the time from date of first dose to date of death due to any cause in Phase Ib. 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 FAS population according to the assigned dose cohort and checkpoint inhibitor in Phase Ib. 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 and checkpoint inhibitor in Phase Ib Kaplan-Meier estimates with 95% confidence intervals every 6 months will be summarized as well by dose level combination, checkpoint inhibitor in Phase Ib and treatment group in Phase II part.

Phase lb: Quantification of [177Lu]Lu-DOTA-TATE excreted from the body in urineWeek 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.

Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-DOTA-TATEWeek 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.

Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-DOTA-TATEWeek 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.

Terminal elimination half-life (T^1/2) of [177Lu]Lu-DOTA-TATEWeek 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.

Phase ll: Objective Response Rate (ORR) by investigator assessmentFrom 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 percentage of participants with confirmed best overall confirmed complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1 by Investigator assessment.

Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs) within 48 hours after [68Ga]Ga-DOTA-TATE administrationup 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.

Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [177Lu]Lu-DOTA-TATEWeek 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.

Terminal-Phase Disposition Rate Constant (λz) of [177Lu]Lu-DOTA-TATEWeek 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.

Preliminary anti-tumor activity of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in newly diagnosed participants with ES-SCLCFrom date of randomisation until date of progression or date of death from any cause, whichever comes first, assessed for up to 3 years (estimated final OS analysis)

Objective response rate defined as the proportion of participants with a best overall confirmed complete response (CR) or partial response (PR) as assessed per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) by Investigator assessment

Trial Locations

Locations (4)

Georgetown University Lombardi Cancer Center

🇺🇸

Washington, District of Columbia, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Novartis Investigative Site

🇬🇧

Guildford, Surrey, United Kingdom

University Hospitals Of Cleveland

🇺🇸

Cleveland, Ohio, United States

Related News

pmc.ncbi.nlm.nih.gov
·

Innovation in Radionuclide Therapy for the Treatment ...

Radionuclide therapies, especially 177Lu-PSMA-617, show promise in treating metastatic castration-resistant prostate cancer (mCRPC), targeting prostate-specific membrane antigen (PSMA) for improved survival. Clinical trials highlight their efficacy and safety, with ongoing research exploring combination therapies and new radionuclides for enhanced treatment outcomes.
© Copyright 2025. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy