Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication LUTATHERA is indicated for the treatment of adult and pediatric patients 12 years and older with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors. FDA label
Also known as [177Lu]Lu-DOTA-TATE, Lu-DOTA-TATE, Lutathera, 177Lu-DOTATATE, 177 Lu-DOTA-Tyr3-Octreotate, 177Lu-DOTA0-Tyr3-Octreotate, Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate, Lutetium Lu 177-DOTA-Tyr3-Octreotate
Lutetium Lu 177 Dotatate · 6 trials · 9 indications
Using the intent to treat (ITT) set and the efficacy analysis set, each ORR will be reported as a point estimate along with a 2-sided 95% exact confidence interval (CI).
To examine whether \[177Lu\]Lu-DOTATATE demonstrates sufficient antitumor activity in patients with recurrent meningioma to justify further investigation. Progression-free survival computed based on MRI-based RANO meningioma response criteria as assessed by the local investigator.
Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC)
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.
To assess efficacy of \[177Lu\]Lu-DOTA-TATE in combination with atezolizumab, carboplatin, and etoposide (experimental arm) versus standard of care consisting of carboplatin, etoposide, and atezolizumab (control arm) in terms of overall survival
A dose-limiting toxicity (DLT) is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that meets any of the criteria defining dose-limiting toxicities and with an onset during the DLT observation period specified for the group. • Group 1: DLT observation period of 49 to 52 days starting from the first administration of \[177Lu\]Lu-DOTA-TATE (Day 1) and ending with the completion of concomitant RT and TMZ. The 49 to 52 days observation period is depending on the start day of concomitant RT and TMZ (i.e. 7-10 days post first \[177Lu\]Lu-DOTA-TATE dose). If the concomitant RT and TMZ is delayed for any reason, the DLT observation period will last until the completion of the concomitant treatment. If RT or TMZ is delayed, the DLT observation period will last until the last administered dose, whichever occurs later.
A dose-limiting toxicity (DLT) is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that meets any of the criteria defining dose-limiting toxicities and with an onset during the DLT observation period specified for the group. • Group 3: DLT observation period of 42 days starting from the first administration of \[177Lu\]Lu-DOTA-TATE (Day 1) i.e. accounting for 2 cycles of Lu\]Lu-DOTA-TATE.
The feasibility of perioperative 177Lu Dotatate as part of the therapeutic regimen to treat metastatic neuroendocrine tumors (NETs) will be assessed on the basis of number and proportion of participants who undergo 2 cycles of complication free 177Lu Dotatate therapy followed by cytoreductive surgery without complications, expressed as a number without dispersion. Complications are defined as follows. * Radiation fibrosis * Hepatic fibrosis by histologic diagnosis * Hepatic insufficiency * Bowel anastamotic leak (if bowel surgery) * Distal pancreatic leak (if pancreas surgery)
| Arm | Type | Description |
|---|---|---|
| Treatment (177Lu-DOTATATE) | EXPERIMENTAL | Patients receive 177Lu-DOTATATE IV over 30-40 minutes during weeks 1, 8, 16, and 24 in the absence of disease progression or unacceptable toxicity. Patients also receive Ga 68-DOTATATE and undergo PET/CT during screening, biopsy as clinically-indicated as well as CT and/or MRI and collection of blood samples throughout the study. |
| Control group: local standard of care (LOC) | ACTIVE_COMPARATOR | According to local standard practice, treatment in the control arm is left to the investigator's discretion. * Hydroxyurea * Bevacizumab * Sunitinib * Octreotide (Sandostatin LAR) * Everolimus * No treatment (observation with regular follow-up and best supportive care) |
| Experimental group: 177Lu-DOTATATE | EXPERIMENTAL | Patients will receive 177Lu-DOTATATE with a total dose of 7.4 GBq/cycle every four (4) weeks for four (4) cycles as an IV infusion |
| 177Lu-DOTATATE | EXPERIMENTAL | A total of two doses of 177Lu-DOTATATE will be administered intravenously. The minimum time between treatments is 2 weeks. |
| Dose Level 1 (DL1) | EXPERIMENTAL | Dose 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) | EXPERIMENTAL | Dose 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) | EXPERIMENTAL | Dose 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) | EXPERIMENTAL | Dose 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) | EXPERIMENTAL | Dose 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) | EXPERIMENTAL | Dose 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 | EXPERIMENTAL | \[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm) |
| Phase II Control arm | OTHER | Carboplatin, etoposide and atezolizumab alone (control arm) |
| Group 1 - Newly diagnosed GB | EXPERIMENTAL | Participants with newly diagnosed glioblastoma will receive \[177Lu\]Lu-DOTA-TATE every 4 weeks +/- 2 days, starting 7 to 10 days prior to initiation of Radiotherapy (RT) and Temozolomide (TMZ) |
| Group 3 - Recurrent GB | EXPERIMENTAL | Participants with recurrent glioblastoma will receive \[177Lu\]Lu-DOTA-TATE as single agent therapy every 3 weeks +/- 2 days |
| Lutathera | EXPERIMENTAL | 2 cycles of 177Lu Dotatate, followed by cytoreductive surgery, followed by additional 177Lu Dotatate (up to 2 cycles) for residual disease as determined by 68Ga DOTA TATE PET/CT |
| Name | Type | Description |
|---|---|---|
| Biopsy | PROCEDURE | Undergo biopsy |
| Biospecimen Collection | PROCEDURE | Undergo collection of blood samples |
| Computed Tomography | PROCEDURE | Undergo PET/CT |
| Gallium Ga 68-DOTATATE | RADIATION | Receive 68Ga |
| Lutetium Lu 177 Dotatate | DRUG | Given IV |
| Positron Emission Tomography | PROCEDURE | Undergo PET/CT |
| Local standard of Care | DRUG | According to local standard practice, treatment or no treatment in the control arm is left to the investigator's discretion. |
| 177Lu-DOTATATE | DRUG | Intravenous injection of 177Lu-DOTATATE |
| [177Lu]Lu-DOTA-TATE | DRUG | 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 |
| Atezolizumab | DRUG | Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period |
| [68Ga]Ga-DOTA-TATE | DRUG | 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) |
| Carboplatin | OTHER | Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period |
| Etoposide | OTHER | Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period |
| Temozolomide | OTHER | Concomitant Phase: Temozolomide 75mg/m2/d p.o until last day of EBRT. Maintenance Phase: Temozolomide p.o 150 mg/m2/d during cycle 1 then 200 mg/m2/d for the following cycles if tolerated well in Cycle 1. 6 cycles total (1 cycle = every 28 days) |
| Radiotherapy | OTHER | 2 Gy/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks |
| Lutathera | DRUG | 4 administrations of 7.4 gigabecquerel (GBq) (200 mCi) 177Lu Dotatate +/ 10% at the date and time of infusion, accumulative dose of 29.6 GBq (800 mCi). T |
| Gallium 68 Dotatate | DRUG | Standard of care, 2 Megabecquerel (MBq)/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi) |
| Computed Tomography (CT) | PROCEDURE | Medical Imaging |
| Magnetic Resonance Imaging (MRI) | PROCEDURE | Medical Imaging |
| PET/CT | PROCEDURE | Medical Imaging |
Inclusion Criteria: * Life expectancy of \> 6 months, as determined by the investigator * Ability to understand and the willingness to sign a written informed consent document * Patients aged \>= 18-100 years old at time of informed consent * Histologically or cytologically confirmed metastatic bre...
Lutetium Lu 177 Dotatate is being studied in several cancers, including recurrent meningioma, extensive stage small cell lung cancer, glioblastoma, recurrent neuroblastoma, and gastroenteropancreatic neuroendocrine tumors. It is an investigational therapy in clinical trials, not yet approved for these uses.
Lutetium Lu 177 Dotatate targets somatostatin receptors, specifically SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5. It is a binding agent that delivers radiation to cells expressing these receptors.
Lutetium Lu 177 Dotatate is being developed by Novartis AG, which trades under the ticker NVS.
Lutetium Lu 177 Dotatate is in Phase 2 clinical development. It is investigational and has not been approved by the FDA for the indications currently being studied.
Lutetium Lu 177 Dotatate is being tested in trials including NCT06326190 for recurrent meningioma, NCT05142696 for extensive stage small cell lung cancer, NCT05109728 for glioblastoma, and NCT04903899 for pediatric neuroblastoma. These studies are actively recruiting or ongoing.
Yes, Lutetium Lu 177 Dotatate is also known as Lutathera, [177Lu]Lu-DOTA-TATE, Lu-DOTA-TATE, and 177Lu-DOTATATE. These names refer to the same compound.