Regulatory Decision Summary for Lutathera

The purpose of the current Supplement to a New Drug Submission (SNDS) is to extend the currently authorised indication of Lutathera (lutetium [¹⁷⁷Lu] oxodotreotide) for the treatment of unresectable or metastatic, well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults with progressive disease to adolescents 12 years of age and older.

Data from NETTER-P, an on-going, multicentre open-label, single arm study to evaluate safety and dosimetry of Lutathera in adolescent patients (aged 12 to <18 years of age) with somatostatin receptor-positive (SSTR+) tumors, including GEP-NET, revealed no new safety signals. Dosimetry assessments were performed after the first dose of Lutathera in NETTER-P following which, pharmacokinetics (PK)/dosimetry modelling was conducted to estimate the cumulative radiation absorbed dose from four (4) doses. The modelling results showed that a dose of 7.4 gigabecquerel (GBq) Lutathera over four (4) cycles (i.e., same dose regimen as for adults) would give a median kidney and bone marrow dosimetry value of 17.4 ± 8.4 grays (Gy) and 0.89 ± 0.59 Gy in the adolescent population, which was below the threshold of 29 Gy and 2 Gy, respectively, established for predisposing patients to toxicity. The probability of exceeding the threshold of 29 Gy for the kidney and 2 Gy for bone marrow in adolescents was estimated to be 21.0% and 2.6%, respectively. To mitigate the potential risk of kidney and/or bone marrow toxicity due to increased radiation exposure, additional dosimetry monitoring and dose reduction recommendations are included in the Lutathera Product Monograph.

The efficacy endpoints evaluated in NETTER-P were exploratory in nature, however, did support evidence of efficacy in the GEP-NET population. The efficacy results from the adult study NETTER-1 were extrapolated to the adolescent GEP-NET population based on the common etiology, prognosis of GEP-NET and the overexpression of the somatostatin-receptor (SSTR) target. Lutathera is expected to be effective and safe in pediatric patients 12 years and older, similar to what is observed in adult patients.

Taken together, the overall benefit-risk profile of the use of Lutathera in the treatment of unresectable or metastatic, well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adolescents 12 years and older with progressive disease is positive. A Notice of Compliance is recommended.

An updated Risk Management Plan (RMP) for Lutathera was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

For further details about Lutathera, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.